Arsenović-Ranin, Nevena

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  • Arsenović-Ranin, Nevena (58)

Author's Bibliography

Normal human microbiota and dysbiosis - implications for health and disease

Božić, Dragana; Milenković, Marina; Antić-Stanković, Jelena; Arsenović-Ranin, Nevena; Bufan, Biljana

(Beograd : Savez farmaceutskih udruženja Srbije, 2024)

TY  - JOUR
AU  - Božić, Dragana
AU  - Milenković, Marina
AU  - Antić-Stanković, Jelena
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5582
AB  - The normal human microbiota, formerly called the "microbial flora," consists of bacteria,
fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory,
gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies
between different body niches and is greatest in the intestinal tract. The microbiota contributes to
the homeostasis of the human organism by preventing colonisation by pathogenic
microorganisms, participating in digestive processes and metabolism, and regulating immune
functions.
Various environmental and genetic factors can lead to an imbalance in the human
microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of
decreased microbial diversity and a lower number of saprophytic microorganisms, followed by
an overgrowth of opportunistic species. The most common diseases directly related to intestinal
dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are
associated with the excessive growth of harmful bacteria and Clostridioides difficile following
broad-spectrum antibiotic therapy.
Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis,
eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic
syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as
Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility,
preterm birth, and malignancies.
AB  - Normalna ljudska mikrobiota, koja se ranije nazivala „mikroflora“, sastoji se od bakterija,
gljivica, virusa i parazita koji kolonizuju kožu i sluzokožu respiratornog, gastrointestinalnog i
genitourinarnog trakta. Broj i raznovrsnost mikroorganizama variraju između različitih telesnih
niša i najveći su u crevnom traktu. Mikrobiota doprinosi homeostazi ljudskog organizma tako što
sprečava kolonizaciju patogenim mikroorganizmima, učestvuje u procesima varenja i
metabolizma i reguliše imunološke funkcije.
Disbioza je stanje u kome dolazi do neravnoteže sastava mikrobiote usled uticaja različitih
egzogenih ili endogenih faktora, što može uticati na ljudsko zdravlje. Ona je najčešće rezultat
smanjene raznovrsnosti mikroorganizama i manjeg broja saprofitnih bakterija, što je praćeno
prekomernim rastom potencijalno štetnih vrsta. Najčešće bolesti koje su direktno povezane sa
crevnom disbiozom su dijareja povezana sa primenom antibiotika i pseudomembranozni kolitis,
a obe nastaju kao posledica prekomernog rasta štetnih bakterija i Clostridioides difficile nakon
terapije antibioticima širokog spektra.
Disbioza je povezana sa različitim zdravstvenim stanjima ili bolestima kao što su akne,
psorijaza, ekcem, hronična opstruktivna bolest pluća, inflamatorna bolest creva, gojaznost,
metabolički sindrom, dijabetes tipa 2, autoimunske bolesti i alergije, neurološke bolesti kao što
su Parkinsonova bolest, Alchajmerova demencija, epilepsija i moždani udar, depresija,
anksioznost, neplodnost, prevremeni porođaj i maligni tumori.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
PB  - Beograd : Univerzitet u Beogradu - Farmaceutski fakultet
T2  - Arhiv za farmaciju
T1  - Normal human microbiota and dysbiosis - implications for health and disease
T1  - Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest
VL  - 74
IS  - 1
SP  - 1
EP  - 22
DO  - 10.5937/arhfarm74-46612
ER  - 
@article{
author = "Božić, Dragana and Milenković, Marina and Antić-Stanković, Jelena and Arsenović-Ranin, Nevena and Bufan, Biljana",
year = "2024",
abstract = "The normal human microbiota, formerly called the "microbial flora," consists of bacteria,
fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory,
gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies
between different body niches and is greatest in the intestinal tract. The microbiota contributes to
the homeostasis of the human organism by preventing colonisation by pathogenic
microorganisms, participating in digestive processes and metabolism, and regulating immune
functions.
Various environmental and genetic factors can lead to an imbalance in the human
microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of
decreased microbial diversity and a lower number of saprophytic microorganisms, followed by
an overgrowth of opportunistic species. The most common diseases directly related to intestinal
dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are
associated with the excessive growth of harmful bacteria and Clostridioides difficile following
broad-spectrum antibiotic therapy.
Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis,
eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic
syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as
Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility,
preterm birth, and malignancies., Normalna ljudska mikrobiota, koja se ranije nazivala „mikroflora“, sastoji se od bakterija,
gljivica, virusa i parazita koji kolonizuju kožu i sluzokožu respiratornog, gastrointestinalnog i
genitourinarnog trakta. Broj i raznovrsnost mikroorganizama variraju između različitih telesnih
niša i najveći su u crevnom traktu. Mikrobiota doprinosi homeostazi ljudskog organizma tako što
sprečava kolonizaciju patogenim mikroorganizmima, učestvuje u procesima varenja i
metabolizma i reguliše imunološke funkcije.
Disbioza je stanje u kome dolazi do neravnoteže sastava mikrobiote usled uticaja različitih
egzogenih ili endogenih faktora, što može uticati na ljudsko zdravlje. Ona je najčešće rezultat
smanjene raznovrsnosti mikroorganizama i manjeg broja saprofitnih bakterija, što je praćeno
prekomernim rastom potencijalno štetnih vrsta. Najčešće bolesti koje su direktno povezane sa
crevnom disbiozom su dijareja povezana sa primenom antibiotika i pseudomembranozni kolitis,
a obe nastaju kao posledica prekomernog rasta štetnih bakterija i Clostridioides difficile nakon
terapije antibioticima širokog spektra.
Disbioza je povezana sa različitim zdravstvenim stanjima ili bolestima kao što su akne,
psorijaza, ekcem, hronična opstruktivna bolest pluća, inflamatorna bolest creva, gojaznost,
metabolički sindrom, dijabetes tipa 2, autoimunske bolesti i alergije, neurološke bolesti kao što
su Parkinsonova bolest, Alchajmerova demencija, epilepsija i moždani udar, depresija,
anksioznost, neplodnost, prevremeni porođaj i maligni tumori.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije, Beograd : Univerzitet u Beogradu - Farmaceutski fakultet",
journal = "Arhiv za farmaciju",
title = "Normal human microbiota and dysbiosis - implications for health and disease, Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest",
volume = "74",
number = "1",
pages = "1-22",
doi = "10.5937/arhfarm74-46612"
}
Božić, D., Milenković, M., Antić-Stanković, J., Arsenović-Ranin, N.,& Bufan, B.. (2024). Normal human microbiota and dysbiosis - implications for health and disease. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 74(1), 1-22.
https://doi.org/10.5937/arhfarm74-46612
Božić D, Milenković M, Antić-Stanković J, Arsenović-Ranin N, Bufan B. Normal human microbiota and dysbiosis - implications for health and disease. in Arhiv za farmaciju. 2024;74(1):1-22.
doi:10.5937/arhfarm74-46612 .
Božić, Dragana, Milenković, Marina, Antić-Stanković, Jelena, Arsenović-Ranin, Nevena, Bufan, Biljana, "Normal human microbiota and dysbiosis - implications for health and disease" in Arhiv za farmaciju, 74, no. 1 (2024):1-22,
https://doi.org/10.5937/arhfarm74-46612 . .

Selenium nanoparticles render pandrug-resistant Acinetobacter baumannii susceptible to colistin

Ušjak, Dušan; Novović, Katarina; Filipić, Brankica; Kojić, Milan; Filipović, Nenad; Stevanović, Magdalena M.; Arsenović-Ranin, Nevena; Milenković, Marina

(Macedonian Pharmaceutical Association, 2022)

TY  - CONF
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena M.
AU  - Arsenović-Ranin, Nevena
AU  - Milenković, Marina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5133
AB  - Colistin is used as a “last resort” drug in the treatment
of carbapenem-resistant Acinetobacter baumannii
infections. Though not the most convenient option due to
the serious side effects, this antibiotic can be very efficient
if administered properly (Garnacho-Montero and Timsit,
2019). However, for several years now, we are witnessing
a steady emergence of colistin-resistant (ColR) strains, with
the constant threat of a sudden burst worldwide (Nowak et
al., 2017). Having in mind that these strains are usually
non-susceptible to any of the existing treatments, i.e.
pandrug-resistant (PDR), the development of new
therapeutic strategies is desperately needed.
In the present study, we showed that colistin
susceptibility of ColR A. baumannii strains can be fully
restored in the presence of very low amounts of selenium
nanoparticles (SeNPs). To demonstrate potent synergistic
interactions between colistin and SeNPs, we performed
checkerboard and time-kill analyses.
PB  - Macedonian Pharmaceutical Association
C3  - Macedonian Pharmaceutical Bulletin
T1  - Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin
VL  - 68
IS  - Suppl. 1
SP  - 295
EP  - 296
DO  - 10.33320/maced.pharm.bull.2022.68.03.142
ER  - 
@conference{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena M. and Arsenović-Ranin, Nevena and Milenković, Marina",
year = "2022",
abstract = "Colistin is used as a “last resort” drug in the treatment
of carbapenem-resistant Acinetobacter baumannii
infections. Though not the most convenient option due to
the serious side effects, this antibiotic can be very efficient
if administered properly (Garnacho-Montero and Timsit,
2019). However, for several years now, we are witnessing
a steady emergence of colistin-resistant (ColR) strains, with
the constant threat of a sudden burst worldwide (Nowak et
al., 2017). Having in mind that these strains are usually
non-susceptible to any of the existing treatments, i.e.
pandrug-resistant (PDR), the development of new
therapeutic strategies is desperately needed.
In the present study, we showed that colistin
susceptibility of ColR A. baumannii strains can be fully
restored in the presence of very low amounts of selenium
nanoparticles (SeNPs). To demonstrate potent synergistic
interactions between colistin and SeNPs, we performed
checkerboard and time-kill analyses.",
publisher = "Macedonian Pharmaceutical Association",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin",
volume = "68",
number = "Suppl. 1",
pages = "295-296",
doi = "10.33320/maced.pharm.bull.2022.68.03.142"
}
Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M. M., Arsenović-Ranin, N.,& Milenković, M.. (2022). Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 68(Suppl. 1), 295-296.
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142
Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović MM, Arsenović-Ranin N, Milenković M. Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin. 2022;68(Suppl. 1):295-296.
doi:10.33320/maced.pharm.bull.2022.68.03.142 .
Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena M., Arsenović-Ranin, Nevena, Milenković, Marina, "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin" in Macedonian Pharmaceutical Bulletin, 68, no. Suppl. 1 (2022):295-296,
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142 . .

B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor

Bufan, Biljana; Arsenović-Ranin, Nevena; Živković, Irena; Petrović, Raisa; Leposavić, Gordana

(Elsevier Inc., 2022)

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Leposavić, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4109
AB  - Aims: Given that deprivation of noradrenaline acting on lymphocytes through β-adrenoceptor influences anti- body response, the effects of propranolol treatment beginning two days before immunization with quadrivalent inactivated influenza vaccine (QIV) on IgG response and underlying cellular molecular mechanism in mice were investigated. Main methods: Twenty-one days post-immunization the total QIV antigen-specific IgG titer and IgG subclass titers in sera were determined using ELISA. Additionally, the total counts of germinal centre (GC) B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in draining lymph nodes (dLNs) and spleens, in vitro prolif- eration of interacting B cells and Th cells and IL-21 synthesis in Th cells in response to QIV antigens and/or mitogen were attested using flow cytometry analysis. In QIV antigen-stimulated dLN cell and splenocyte cultures were also measured concentrations of INF-γ and IL-4, cytokines upregulating IgG2a and IgG1 synthesis, respectively. Key findings: Propranolol decreased the total QIV antigen-specific IgG titer. This correlated with lower GC B cell count and the shift in Tfr/Tfh cell and Tfr/GC B cell ratio towards Tfr in propranolol-treated mice compared with controls. Consistently, QIV antigen-stimulated proliferation of B cells and Th cells from propranolol-treated mice in vitro was impaired. This correlated with the lower frequency of QIV antigen-specific IL-21-producing cells among Th cells. Additionally, in propranolol-treated mice, in accordance with the changes in INF-γ/IL-4 ratio in dLN cell/splenocyte cultures, serum IgG2a/IgG1 ratio was shifted towards IgG1 reflecting decreased IgG2a response. Significance: The study indicates that chronic propranolol treatment may impair response to QIV.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor
VL  - 301
DO  - 10.1016/j.lfs.2022.120617
ER  - 
@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Petrović, Raisa and Leposavić, Gordana",
year = "2022",
abstract = "Aims: Given that deprivation of noradrenaline acting on lymphocytes through β-adrenoceptor influences anti- body response, the effects of propranolol treatment beginning two days before immunization with quadrivalent inactivated influenza vaccine (QIV) on IgG response and underlying cellular molecular mechanism in mice were investigated. Main methods: Twenty-one days post-immunization the total QIV antigen-specific IgG titer and IgG subclass titers in sera were determined using ELISA. Additionally, the total counts of germinal centre (GC) B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in draining lymph nodes (dLNs) and spleens, in vitro prolif- eration of interacting B cells and Th cells and IL-21 synthesis in Th cells in response to QIV antigens and/or mitogen were attested using flow cytometry analysis. In QIV antigen-stimulated dLN cell and splenocyte cultures were also measured concentrations of INF-γ and IL-4, cytokines upregulating IgG2a and IgG1 synthesis, respectively. Key findings: Propranolol decreased the total QIV antigen-specific IgG titer. This correlated with lower GC B cell count and the shift in Tfr/Tfh cell and Tfr/GC B cell ratio towards Tfr in propranolol-treated mice compared with controls. Consistently, QIV antigen-stimulated proliferation of B cells and Th cells from propranolol-treated mice in vitro was impaired. This correlated with the lower frequency of QIV antigen-specific IL-21-producing cells among Th cells. Additionally, in propranolol-treated mice, in accordance with the changes in INF-γ/IL-4 ratio in dLN cell/splenocyte cultures, serum IgG2a/IgG1 ratio was shifted towards IgG1 reflecting decreased IgG2a response. Significance: The study indicates that chronic propranolol treatment may impair response to QIV.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor",
volume = "301",
doi = "10.1016/j.lfs.2022.120617"
}
Bufan, B., Arsenović-Ranin, N., Živković, I., Petrović, R.,& Leposavić, G.. (2022). B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor. in Life Sciences
Elsevier Inc.., 301.
https://doi.org/10.1016/j.lfs.2022.120617
Bufan B, Arsenović-Ranin N, Živković I, Petrović R, Leposavić G. B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor. in Life Sciences. 2022;301.
doi:10.1016/j.lfs.2022.120617 .
Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Petrović, Raisa, Leposavić, Gordana, "B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor" in Life Sciences, 301 (2022),
https://doi.org/10.1016/j.lfs.2022.120617 . .
2
1
1

β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice

Bufan, Biljana; Arsenović-Ranin, Nevena; Petrović, Raisa; Živković, Irena; Leposavić, Gordana

(2021)

TY  - CONF
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Leposavić, Gordana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4725
AB  - The study was undertaken considering importance of antibody response for influenza vaccine efficacy and data indicating that β2‐adrenoceptor stimulation may affect antibody generation. To elucidate influence of β‐adrenoceptor‐mediated signaling on antibody response to QIV, serum titers of QIV‐specific IgG and draining lymph node and splenic germinal center (GC) reaction to QIV were examined in BALB/c mice treated with propranolol, non‐selective β‐adrenoceptor blocker, or vehicle (controls) daily, beginning two days before immunization. Four weeks after immunization IgG antibody titer was decreased in propranolol‐treated mice. This correlated with lower frequency of GC B cells in lymphoid organs of propranolol‐treated mice, and their diminished proliferation upon restimulation with QIV antigens in culture. Consistently, Tfh/Tfr cell ratio was shifted towards the latter in propranolol‐treated mice. This correlated with lower frequency of QIV‐specific CD4+ cells that produce IL‐21, the key regulator of GC reaction, in lymphoid organs of propranolol‐ 
treated mice, as suggested by in vitro recall test. Additionally, propranolol treatment shifted IgG1/IgG2a antibody ratio towards IgG1 antibody (contributing mainly to the virus clearance). This was consistent with the shift in IFN‐γ/IL‐4 ratio to the site of IL‐4 in QIV‐stimulated splenocyte cultures from propranolol‐treated mice compared with controls. Thus, the study suggests that chronic administration of propranolol, drug widely used for cardiovascular pathology, and recently repurposed for several other pathologies, including cancer, rheumatoid arthritis, and anxiety may impair efficacy of QIV by affecting CD4+ T‐cell cytokine secretory profile and thereby overall efficacy of Tfh help to B cells, and its influence on IgG subclass switching pattern.
C3  - European Journal of Immunology
T1  - β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice
VL  - 51
IS  - Suppl.1
SP  - 305
EP  - 305
DO  - 10.1002/eji.202170200
ER  - 
@conference{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Leposavić, Gordana",
year = "2021",
abstract = "The study was undertaken considering importance of antibody response for influenza vaccine efficacy and data indicating that β2‐adrenoceptor stimulation may affect antibody generation. To elucidate influence of β‐adrenoceptor‐mediated signaling on antibody response to QIV, serum titers of QIV‐specific IgG and draining lymph node and splenic germinal center (GC) reaction to QIV were examined in BALB/c mice treated with propranolol, non‐selective β‐adrenoceptor blocker, or vehicle (controls) daily, beginning two days before immunization. Four weeks after immunization IgG antibody titer was decreased in propranolol‐treated mice. This correlated with lower frequency of GC B cells in lymphoid organs of propranolol‐treated mice, and their diminished proliferation upon restimulation with QIV antigens in culture. Consistently, Tfh/Tfr cell ratio was shifted towards the latter in propranolol‐treated mice. This correlated with lower frequency of QIV‐specific CD4+ cells that produce IL‐21, the key regulator of GC reaction, in lymphoid organs of propranolol‐ 
treated mice, as suggested by in vitro recall test. Additionally, propranolol treatment shifted IgG1/IgG2a antibody ratio towards IgG1 antibody (contributing mainly to the virus clearance). This was consistent with the shift in IFN‐γ/IL‐4 ratio to the site of IL‐4 in QIV‐stimulated splenocyte cultures from propranolol‐treated mice compared with controls. Thus, the study suggests that chronic administration of propranolol, drug widely used for cardiovascular pathology, and recently repurposed for several other pathologies, including cancer, rheumatoid arthritis, and anxiety may impair efficacy of QIV by affecting CD4+ T‐cell cytokine secretory profile and thereby overall efficacy of Tfh help to B cells, and its influence on IgG subclass switching pattern.",
journal = "European Journal of Immunology",
title = "β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice",
volume = "51",
number = "Suppl.1",
pages = "305-305",
doi = "10.1002/eji.202170200"
}
Bufan, B., Arsenović-Ranin, N., Petrović, R., Živković, I.,& Leposavić, G.. (2021). β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice. in European Journal of Immunology, 51(Suppl.1), 305-305.
https://doi.org/10.1002/eji.202170200
Bufan B, Arsenović-Ranin N, Petrović R, Živković I, Leposavić G. β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice. in European Journal of Immunology. 2021;51(Suppl.1):305-305.
doi:10.1002/eji.202170200 .
Bufan, Biljana, Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Leposavić, Gordana, "β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice" in European Journal of Immunology, 51, no. Suppl.1 (2021):305-305,
https://doi.org/10.1002/eji.202170200 . .
156
3

Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases

Stojić-Vukanić, Zorica; Pilipović, Ivan; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

(Elsevier B.V., 2021)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3946
AB  - The incidence of multiple sclerosis (MS) and susceptibility of animals to experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, decrease with aging. Generally, autoimmune diseases develop as the ultimate outcome of an imbalance between damaging immune responses against self and regulatory immune responses (keeping the former under control). Thus, in this review the age-related changes possibly underlying this balance were discussed. Specifically, considering the central role of T cells in MS/EAE, the impact of aging on overall functional capacity (reflecting both overall count and individual functional cell properties) of self-reactive conventional T cells (Tcons) and FoxP3+ regulatory T cells (Tregs), as the most potent immunoregulatory/suppressive cells, was analyzed, as well. The analysis encompasses three distinct compartments: thymus (the primary lymphoid organ responsible for the elimination of self-reactive T cells – negative selection and the generation of Tregs, compensating for imperfections of the negative selection), peripheral blood/lymphoid tissues (“afferent” compartment), and brain/spinal cord tissues (“target” compartment). Given that the incidence of MS and susceptibility of animals to EAE are greater in women/females than in age-matched men/males, sex as independent variable was also considered. In conclusion, with aging, sex-specific alterations in the balance of self-reactive Tcons/Tregs are likely to occur not only in the thymus/”afferent” compartment, but also in the “target” compartment, reflecting multifaceted changes in both T-cell types. Their in depth understanding is important not only for envisaging effects of aging, but also for designing interventions to slow-down aging without any adverse effect on incidence of autoimmune diseases.
PB  - Elsevier B.V.
T2  - Immunology Letters
T1  - Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases
VL  - 239
SP  - 42
EP  - 59
DO  - 10.1016/j.imlet.2021.08.003
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2021",
abstract = "The incidence of multiple sclerosis (MS) and susceptibility of animals to experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, decrease with aging. Generally, autoimmune diseases develop as the ultimate outcome of an imbalance between damaging immune responses against self and regulatory immune responses (keeping the former under control). Thus, in this review the age-related changes possibly underlying this balance were discussed. Specifically, considering the central role of T cells in MS/EAE, the impact of aging on overall functional capacity (reflecting both overall count and individual functional cell properties) of self-reactive conventional T cells (Tcons) and FoxP3+ regulatory T cells (Tregs), as the most potent immunoregulatory/suppressive cells, was analyzed, as well. The analysis encompasses three distinct compartments: thymus (the primary lymphoid organ responsible for the elimination of self-reactive T cells – negative selection and the generation of Tregs, compensating for imperfections of the negative selection), peripheral blood/lymphoid tissues (“afferent” compartment), and brain/spinal cord tissues (“target” compartment). Given that the incidence of MS and susceptibility of animals to EAE are greater in women/females than in age-matched men/males, sex as independent variable was also considered. In conclusion, with aging, sex-specific alterations in the balance of self-reactive Tcons/Tregs are likely to occur not only in the thymus/”afferent” compartment, but also in the “target” compartment, reflecting multifaceted changes in both T-cell types. Their in depth understanding is important not only for envisaging effects of aging, but also for designing interventions to slow-down aging without any adverse effect on incidence of autoimmune diseases.",
publisher = "Elsevier B.V.",
journal = "Immunology Letters",
title = "Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases",
volume = "239",
pages = "42-59",
doi = "10.1016/j.imlet.2021.08.003"
}
Stojić-Vukanić, Z., Pilipović, I., Arsenović-Ranin, N., Dimitrijević, M.,& Leposavić, G.. (2021). Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases. in Immunology Letters
Elsevier B.V.., 239, 42-59.
https://doi.org/10.1016/j.imlet.2021.08.003
Stojić-Vukanić Z, Pilipović I, Arsenović-Ranin N, Dimitrijević M, Leposavić G. Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases. in Immunology Letters. 2021;239:42-59.
doi:10.1016/j.imlet.2021.08.003 .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Leposavić, Gordana, "Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases" in Immunology Letters, 239 (2021):42-59,
https://doi.org/10.1016/j.imlet.2021.08.003 . .
1

Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Bufan, Biljana; Nacka-Aleksić, Mirjana; Kosec, Dušan; Pilipović, Ivan; Kotur-Stevuljević, Jelena; Simić, Ljubica; Sopta, Jelena; Leposavić, Gordana

(Springer Nature, 2020)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Dušan
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Simić, Ljubica
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3714
AB  - Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
PB  - Springer Nature
T2  - Inflammation
T1  - Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats
VL  - 43
IS  - 6
SP  - 2312
EP  - 2331
DO  - 10.1007/s10753-020-01302-0
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Kosec, Dušan and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Simić, Ljubica and Sopta, Jelena and Leposavić, Gordana",
year = "2020",
abstract = "Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.",
publisher = "Springer Nature",
journal = "Inflammation",
title = "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats",
volume = "43",
number = "6",
pages = "2312-2331",
doi = "10.1007/s10753-020-01302-0"
}
Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Kosec, D., Pilipović, I., Kotur-Stevuljević, J., Simić, L., Sopta, J.,& Leposavić, G.. (2020). Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats. in Inflammation
Springer Nature., 43(6), 2312-2331.
https://doi.org/10.1007/s10753-020-01302-0
Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Kosec D, Pilipović I, Kotur-Stevuljević J, Simić L, Sopta J, Leposavić G. Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats. in Inflammation. 2020;43(6):2312-2331.
doi:10.1007/s10753-020-01302-0 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Kosec, Dušan, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Simić, Ljubica, Sopta, Jelena, Leposavić, Gordana, "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats" in Inflammation, 43, no. 6 (2020):2312-2331,
https://doi.org/10.1007/s10753-020-01302-0 . .
3
1
3

Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Springer Nature, 2020)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3504
AB  - The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis
VL  - 10
IS  - 1
DO  - 10.1038/s41598-020-58127-y
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2020",
abstract = "The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis",
volume = "10",
number = "1",
doi = "10.1038/s41598-020-58127-y"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2020). Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports
Springer Nature., 10(1).
https://doi.org/10.1038/s41598-020-58127-y
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports. 2020;10(1).
doi:10.1038/s41598-020-58127-y .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis" in Scientific Reports, 10, no. 1 (2020),
https://doi.org/10.1038/s41598-020-58127-y . .
10
25
12
22

Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences

Bufan, Biljana; Arsenović-Ranin, Nevena; Petrović, Raisa; Živković, Irena; Stoiljković, Vera; Leposavić, Gordana

(Elsevier, 2020)

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3521
AB  - Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The age-related decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4+ cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4+ splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Th1/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-γ/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.
PB  - Elsevier
T2  - Experimental Gerontology
T1  - Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences
VL  - 133
DO  - 10.1016/j.exger.2020.110857
ER  - 
@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Stoiljković, Vera and Leposavić, Gordana",
year = "2020",
abstract = "Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The age-related decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4+ cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4+ splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Th1/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-γ/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.",
publisher = "Elsevier",
journal = "Experimental Gerontology",
title = "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences",
volume = "133",
doi = "10.1016/j.exger.2020.110857"
}
Bufan, B., Arsenović-Ranin, N., Petrović, R., Živković, I., Stoiljković, V.,& Leposavić, G.. (2020). Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology
Elsevier., 133.
https://doi.org/10.1016/j.exger.2020.110857
Bufan B, Arsenović-Ranin N, Petrović R, Živković I, Stoiljković V, Leposavić G. Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology. 2020;133.
doi:10.1016/j.exger.2020.110857 .
Bufan, Biljana, Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Stoiljković, Vera, Leposavić, Gordana, "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences" in Experimental Gerontology, 133 (2020),
https://doi.org/10.1016/j.exger.2020.110857 . .
1
5
3
5

Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, 2019)

TY  - CONF
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5087
AB  - Collagen-induced arthritis (CIA) is a well-established experimental model mimicking 
many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including 
sexual dimorphism in the clinical presentation. Our previous study showed that a more 
severe disease in female compared with male rats correlated with more robust Th17 
response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that 
autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in 
the present study the germinal center (GC) reaction in the lymph nodes draining 
inflamed joints and adjacent tissue (dLNs) was examined for putative sexual 
dimorphism. Female rats mounted greater serum collagen II-specific IgG response than 
their male counterparts. This dimorphism correlated with the higher frequency of GC 
B cells in female compared with male dLNs. Consistently, the frequency of 
activated/proliferating Ki67+ cells among dLN B cells was higher in females than in 
males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T 
follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of 
CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell 
frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. 
Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio 
was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and 
protective IgG1 collagen II-specific antibodies was shifted towards the former in 
females. Thus, the study suggests that targeting T/B cell interactions should be 
considered in further translation research aimed to design sex-specific therapies for RA.
PB  - Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book
T1  - Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5087
ER  - 
@conference{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen-induced arthritis (CIA) is a well-established experimental model mimicking 
many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including 
sexual dimorphism in the clinical presentation. Our previous study showed that a more 
severe disease in female compared with male rats correlated with more robust Th17 
response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that 
autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in 
the present study the germinal center (GC) reaction in the lymph nodes draining 
inflamed joints and adjacent tissue (dLNs) was examined for putative sexual 
dimorphism. Female rats mounted greater serum collagen II-specific IgG response than 
their male counterparts. This dimorphism correlated with the higher frequency of GC 
B cells in female compared with male dLNs. Consistently, the frequency of 
activated/proliferating Ki67+ cells among dLN B cells was higher in females than in 
males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T 
follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of 
CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell 
frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. 
Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio 
was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and 
protective IgG1 collagen II-specific antibodies was shifted towards the former in 
females. Thus, the study suggests that targeting T/B cell interactions should be 
considered in further translation research aimed to design sex-specific therapies for RA.",
publisher = "Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book",
title = "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5087"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book
Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia..
https://hdl.handle.net/21.15107/rcub_farfar_5087
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5087 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells" in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5087 .

Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?

Vujnović, Ivana; Pilipović, Ivan; Jasnić, Nebojša; Petrović, Raisa; Blagojević, Veljko; Arsenović-Ranin, Nevena; Stojić-Vukanić, Zorica; Đorđević, Jelena; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Jasnić, Nebojša
AU  - Petrović, Raisa
AU  - Blagojević, Veljko
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3323
AB  - Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Cellular Immunology
T1  - Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?
VL  - 336
SP  - 48
EP  - 57
DO  - 10.1016/j.cellimm.2018.12.009
ER  - 
@article{
author = "Vujnović, Ivana and Pilipović, Ivan and Jasnić, Nebojša and Petrović, Raisa and Blagojević, Veljko and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Đorđević, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Cellular Immunology",
title = "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?",
volume = "336",
pages = "48-57",
doi = "10.1016/j.cellimm.2018.12.009"
}
Vujnović, I., Pilipović, I., Jasnić, N., Petrović, R., Blagojević, V., Arsenović-Ranin, N., Stojić-Vukanić, Z., Đorđević, J.,& Leposavić, G.. (2019). Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology
Academic Press Inc Elsevier Science, San Diego., 336, 48-57.
https://doi.org/10.1016/j.cellimm.2018.12.009
Vujnović I, Pilipović I, Jasnić N, Petrović R, Blagojević V, Arsenović-Ranin N, Stojić-Vukanić Z, Đorđević J, Leposavić G. Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology. 2019;336:48-57.
doi:10.1016/j.cellimm.2018.12.009 .
Vujnović, Ivana, Pilipović, Ivan, Jasnić, Nebojša, Petrović, Raisa, Blagojević, Veljko, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Đorđević, Jelena, Leposavić, Gordana, "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?" in Cellular Immunology, 336 (2019):48-57,
https://doi.org/10.1016/j.cellimm.2018.12.009 . .
1
14
9
13

Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3295
AB  - Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis
VL  - 76
SP  - 198
EP  - 214
DO  - 10.1016/j.bbi.2018.11.311
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis",
volume = "76",
pages = "198-214",
doi = "10.1016/j.bbi.2018.11.311"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 76, 198-214.
https://doi.org/10.1016/j.bbi.2018.11.311
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity. 2019;76:198-214.
doi:10.1016/j.bbi.2018.11.311 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis" in Brain Behavior and Immunity, 76 (2019):198-214,
https://doi.org/10.1016/j.bbi.2018.11.311 . .
4
18
12
19

New vaccines on the horizon

Arsenović-Ranin, Nevena

(Beograd : Savez farmaceutskih udruženja Srbije, 2019)

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3556
AB  - Vaccines are considered to be one of the greatest public health achievements of the last century. As a result of widespread vaccine use, the smallpox virus has been completely eradicated and the incidence of other diseases such as polio, measles, tetanus and diphtheria has been drastically reduced. Current licensed vaccines, predominantly composed of either live attenuated or killed pathogens, pathogen subunits, owe their success to their ability to elicit neutralizing antibodies against pathogens. On the other side, cell-mediated immunity, which plays a central role in elimination of intracellular pathogens (which in most cases leads to chronic infections) is much more difficult to obtain using current vaccines. Currently, numerous vector and nucleic acid (DNA and mRNA)-based prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies, with promising results. This review focuses the background of vector and nucleic acid-based vaccines, their strengths and weaknesses and safety issues.
AB  - Vakcine se smatraju jednim od najvećih javnozdravstvenih dostignuća prošlog veka. Zahvaljujući vakcinaciji u svetu su potpuno iskorenjene velike boginje, a incidencija drugih infektivnih bolesti, kao što su dečija paraliza, male boginje, tetanus i difterija, drastično je smanjena. Današnje licencirane vakcine, koje pretežno sadrže žive atenuisane ili mrtve patogene ili njihove delove, su uspešne zahvaljujući tome što stimulišu produkciju neutrališućih antitela. Sa druge strane, ove vakcine mnogo teže indukuju ćelijski-posredovanu imunost, koja je važna za eliminaciju intraćelijskih patogena (koji često dovode do hroničnih infekcija). Trenutno se u pretkliničkim i kliničkim studijama ispituju brojne profilaktičke vakcine zasnovane na vektorima i nukleinskim kiselinama (DNK i iRNK), sposobne da indukuju snažan odgovor T-ćelija na vakcinalni antigen, sa obećavajućim rezultatima. U ovom radu su date osnovne informacije o vakcinama sa vektorima i nukleinskim kiselinama, opisani su mehanizmi kojima one pokreću imunski odgovor, njihove dobre i loše strane, kao i problemi vezani za njihovu bezbednu primenu.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - New vaccines on the horizon
T1  - Perspektive u razvoju profilaktičkih vakcina
VL  - 69
IS  - 6
SP  - 385
EP  - 405
DO  - 10.5937/arhfarm1906385A
ER  - 
@article{
author = "Arsenović-Ranin, Nevena",
year = "2019",
abstract = "Vaccines are considered to be one of the greatest public health achievements of the last century. As a result of widespread vaccine use, the smallpox virus has been completely eradicated and the incidence of other diseases such as polio, measles, tetanus and diphtheria has been drastically reduced. Current licensed vaccines, predominantly composed of either live attenuated or killed pathogens, pathogen subunits, owe their success to their ability to elicit neutralizing antibodies against pathogens. On the other side, cell-mediated immunity, which plays a central role in elimination of intracellular pathogens (which in most cases leads to chronic infections) is much more difficult to obtain using current vaccines. Currently, numerous vector and nucleic acid (DNA and mRNA)-based prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies, with promising results. This review focuses the background of vector and nucleic acid-based vaccines, their strengths and weaknesses and safety issues., Vakcine se smatraju jednim od najvećih javnozdravstvenih dostignuća prošlog veka. Zahvaljujući vakcinaciji u svetu su potpuno iskorenjene velike boginje, a incidencija drugih infektivnih bolesti, kao što su dečija paraliza, male boginje, tetanus i difterija, drastično je smanjena. Današnje licencirane vakcine, koje pretežno sadrže žive atenuisane ili mrtve patogene ili njihove delove, su uspešne zahvaljujući tome što stimulišu produkciju neutrališućih antitela. Sa druge strane, ove vakcine mnogo teže indukuju ćelijski-posredovanu imunost, koja je važna za eliminaciju intraćelijskih patogena (koji često dovode do hroničnih infekcija). Trenutno se u pretkliničkim i kliničkim studijama ispituju brojne profilaktičke vakcine zasnovane na vektorima i nukleinskim kiselinama (DNK i iRNK), sposobne da indukuju snažan odgovor T-ćelija na vakcinalni antigen, sa obećavajućim rezultatima. U ovom radu su date osnovne informacije o vakcinama sa vektorima i nukleinskim kiselinama, opisani su mehanizmi kojima one pokreću imunski odgovor, njihove dobre i loše strane, kao i problemi vezani za njihovu bezbednu primenu.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "New vaccines on the horizon, Perspektive u razvoju profilaktičkih vakcina",
volume = "69",
number = "6",
pages = "385-405",
doi = "10.5937/arhfarm1906385A"
}
Arsenović-Ranin, N.. (2019). New vaccines on the horizon. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 69(6), 385-405.
https://doi.org/10.5937/arhfarm1906385A
Arsenović-Ranin N. New vaccines on the horizon. in Arhiv za farmaciju. 2019;69(6):385-405.
doi:10.5937/arhfarm1906385A .
Arsenović-Ranin, Nevena, "New vaccines on the horizon" in Arhiv za farmaciju, 69, no. 6 (2019):385-405,
https://doi.org/10.5937/arhfarm1906385A . .

Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences

Arsenović-Ranin, Nevena; Petrović, Raisa; Živković, Irena; Bufan, Biljana; Stoiljković, Vera; Leposavić, Gordana

(Springer, New York, 2019)

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Bufan, Biljana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3266
AB  - The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.
PB  - Springer, New York
T2  - Biogerontology
T1  - Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences
VL  - 20
IS  - 4
SP  - 475
EP  - 496
DO  - 10.1007/s10522-019-09811-8
ER  - 
@article{
author = "Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Bufan, Biljana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences",
volume = "20",
number = "4",
pages = "475-496",
doi = "10.1007/s10522-019-09811-8"
}
Arsenović-Ranin, N., Petrović, R., Živković, I., Bufan, B., Stoiljković, V.,& Leposavić, G.. (2019). Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology
Springer, New York., 20(4), 475-496.
https://doi.org/10.1007/s10522-019-09811-8
Arsenović-Ranin N, Petrović R, Živković I, Bufan B, Stoiljković V, Leposavić G. Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology. 2019;20(4):475-496.
doi:10.1007/s10522-019-09811-8 .
Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Bufan, Biljana, Stoiljković, Vera, Leposavić, Gordana, "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences" in Biogerontology, 20, no. 4 (2019):475-496,
https://doi.org/10.1007/s10522-019-09811-8 . .
1
16
11
15

Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis

Stojić-Vukanić, Zorica; Pilipović, Ivan; Đikić, Jasmina; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Bufan, Biljana; Arsenović-Ranin, Nevena; Kosec, Duško; Leposavić, Gordana

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Đikić, Jasmina
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3188
AB  - The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis
VL  - 101
SP  - 37
EP  - 53
DO  - 10.1016/j.exger.2017.11.002
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Đikić, Jasmina and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Bufan, Biljana and Arsenović-Ranin, Nevena and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis",
volume = "101",
pages = "37-53",
doi = "10.1016/j.exger.2017.11.002"
}
Stojić-Vukanić, Z., Pilipović, I., Đikić, J., Vujnović, I., Nacka-Aleksić, M., Bufan, B., Arsenović-Ranin, N., Kosec, D.,& Leposavić, G.. (2018). Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 101, 37-53.
https://doi.org/10.1016/j.exger.2017.11.002
Stojić-Vukanić Z, Pilipović I, Đikić J, Vujnović I, Nacka-Aleksić M, Bufan B, Arsenović-Ranin N, Kosec D, Leposavić G. Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology. 2018;101:37-53.
doi:10.1016/j.exger.2017.11.002 .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Đikić, Jasmina, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Bufan, Biljana, Arsenović-Ranin, Nevena, Kosec, Duško, Leposavić, Gordana, "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis" in Experimental Gerontology, 101 (2018):37-53,
https://doi.org/10.1016/j.exger.2017.11.002 . .
8
5
8

Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Bufan, Biljana; Nacka-Aleksić, Mirjana; Lazarević-Macanović, Mirjana; Milovanović, Petar; Durić, Marija; Sopta, Jelena; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2018)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Lazarević-Macanović, Mirjana
AU  - Milovanović, Petar
AU  - Durić, Marija
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3220
AB  - Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-gamma + and IL-17 + IFN-gamma + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3 + T regulatory cells (Treg) did not differ between sexes. Thus, CD4 + Teff cells/Treg ratio, and IL-17 + T cells/Treg and IFN-gamma + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4 + T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-gamma-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Experimental and Molecular Pathology
T1  - Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease
VL  - 105
IS  - 1
SP  - 10
EP  - 22
DO  - 10.1016/j.yexmp.2018.05.007
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Lazarević-Macanović, Mirjana and Milovanović, Petar and Durić, Marija and Sopta, Jelena and Leposavić, Gordana",
year = "2018",
abstract = "Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-gamma + and IL-17 + IFN-gamma + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3 + T regulatory cells (Treg) did not differ between sexes. Thus, CD4 + Teff cells/Treg ratio, and IL-17 + T cells/Treg and IFN-gamma + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4 + T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-gamma-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Experimental and Molecular Pathology",
title = "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease",
volume = "105",
number = "1",
pages = "10-22",
doi = "10.1016/j.yexmp.2018.05.007"
}
Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Lazarević-Macanović, M., Milovanović, P., Durić, M., Sopta, J.,& Leposavić, G.. (2018). Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease. in Experimental and Molecular Pathology
Academic Press Inc Elsevier Science, San Diego., 105(1), 10-22.
https://doi.org/10.1016/j.yexmp.2018.05.007
Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Lazarević-Macanović M, Milovanović P, Durić M, Sopta J, Leposavić G. Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease. in Experimental and Molecular Pathology. 2018;105(1):10-22.
doi:10.1016/j.yexmp.2018.05.007 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Lazarević-Macanović, Mirjana, Milovanović, Petar, Durić, Marija, Sopta, Jelena, Leposavić, Gordana, "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease" in Experimental and Molecular Pathology, 105, no. 1 (2018):10-22,
https://doi.org/10.1016/j.yexmp.2018.05.007 . .
1
8
7
8

Mouse strain and sex as determinants of immune response to trivalent influenza vaccine

Petrović, Raisa; Bufan, Biljana; Arsenović-Ranin, Nevena; Živković, Irena; Minić, Rajna; Radojević, Katarina; Leposavić, Gordana

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Petrović, Raisa
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Minić, Rajna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3216
AB  - Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Mouse strain and sex as determinants of immune response to trivalent influenza vaccine
VL  - 207
SP  - 117
EP  - 126
DO  - 10.1016/j.lfs.2018.05.056
ER  - 
@article{
author = "Petrović, Raisa and Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Minić, Rajna and Radojević, Katarina and Leposavić, Gordana",
year = "2018",
abstract = "Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine",
volume = "207",
pages = "117-126",
doi = "10.1016/j.lfs.2018.05.056"
}
Petrović, R., Bufan, B., Arsenović-Ranin, N., Živković, I., Minić, R., Radojević, K.,& Leposavić, G.. (2018). Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 207, 117-126.
https://doi.org/10.1016/j.lfs.2018.05.056
Petrović R, Bufan B, Arsenović-Ranin N, Živković I, Minić R, Radojević K, Leposavić G. Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences. 2018;207:117-126.
doi:10.1016/j.lfs.2018.05.056 .
Petrović, Raisa, Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Minić, Rajna, Radojević, Katarina, Leposavić, Gordana, "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine" in Life Sciences, 207 (2018):117-126,
https://doi.org/10.1016/j.lfs.2018.05.056 . .
3
15
9
14

Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type

Živković, Irena; Petrović, Raisa; Arsenović-Ranin, Nevena; Petrusić, Vladimir; Minić, Rajna; Bufan, Biljana; Popović, Olga; Leposavić, Gordana

(Academic Press Ltd- Elsevier Science Ltd, London, 2018)

TY  - JOUR
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Petrusić, Vladimir
AU  - Minić, Rajna
AU  - Bufan, Biljana
AU  - Popović, Olga
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3160
AB  - The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Biologicals
T1  - Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type
VL  - 52
SP  - 18
EP  - 24
DO  - 10.1016/j.biologicals.2018.01.007
ER  - 
@article{
author = "Živković, Irena and Petrović, Raisa and Arsenović-Ranin, Nevena and Petrusić, Vladimir and Minić, Rajna and Bufan, Biljana and Popović, Olga and Leposavić, Gordana",
year = "2018",
abstract = "The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Biologicals",
title = "Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type",
volume = "52",
pages = "18-24",
doi = "10.1016/j.biologicals.2018.01.007"
}
Živković, I., Petrović, R., Arsenović-Ranin, N., Petrusić, V., Minić, R., Bufan, B., Popović, O.,& Leposavić, G.. (2018). Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type. in Biologicals
Academic Press Ltd- Elsevier Science Ltd, London., 52, 18-24.
https://doi.org/10.1016/j.biologicals.2018.01.007
Živković I, Petrović R, Arsenović-Ranin N, Petrusić V, Minić R, Bufan B, Popović O, Leposavić G. Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type. in Biologicals. 2018;52:18-24.
doi:10.1016/j.biologicals.2018.01.007 .
Živković, Irena, Petrović, Raisa, Arsenović-Ranin, Nevena, Petrusić, Vladimir, Minić, Rajna, Bufan, Biljana, Popović, Olga, Leposavić, Gordana, "Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type" in Biologicals, 52 (2018):18-24,
https://doi.org/10.1016/j.biologicals.2018.01.007 . .
21
15
19

Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy

Arsenović-Ranin, Nevena; Kosec, Duško; Pilipović, Ivan; Nacka-Aleksić, Mirjana; Bufan, Biljana; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Springer, Dordrecht, 2017)

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2898
AB  - The study examined the influence of age, sex and peripubertal gonadectomy on a set of T-cell phenotypic parameters. Rats of both sexes were gonadectomised at the age of 1 month and peripheral blood and spleen T lymphocytes from non-gonadectomised and gonadectomised 3- and 11-month-old rats were examined for the expression of differentiation/activation (CD90/CD45RC) and immunoregulatory markers. Peripheral blood T lymphocytes from non-gonadectomised rats showed age-dependent sexual dimorphisms in (1) total count (lower in female than male 11-month-old rats); (2) CD4+:CD8 + cell ratio (higher in female than male rats of both ages); (3) the proportion of recent thymic emigrants in CD8 + T cells (lower in female than male 3-month-old rats) and (4) the proportions of mature na  lt  ve and memory/activated cells (irrespective of age, the proportion of na  lt  ve cells was higher, whereas that of memory/activated cells was lower in females). Gonadectomy influenced magnitudes or direction of these sex differences. Additionally, sex differences in peripheral blood T-lymphocyte parameters did not fully correspond to those observed in T-splenocyte parameters, suggesting the compartment-specific regulation of the major T-cell subpopulations' and their subsets' composition. Furthermore, there was no sexual dimorphism in the proportion of either CD25 + Foxp3 + cells among CD4 + or CD161+ (NKT) cells within CD8 + T lymphocytes. However, there was gonadal hormone-independent age-associated sexual dimorphism in the proportion of CD161 + cells (NKT cells) in CD8 + T splenocytes. Overall, the study revealed age-dependent variations in sexual dimorphisms in T-cell parameters relevant for immune response efficacy and showed that they are T-cell compartment-specific and partly gonadal hormone-related.
PB  - Springer, Dordrecht
T2  - Molecular and Cellular Biochemistry
T1  - Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy
VL  - 431
IS  - 1-2
SP  - 169
EP  - 185
DO  - 10.1007/s11010-017-2989-x
ER  - 
@article{
author = "Arsenović-Ranin, Nevena and Kosec, Duško and Pilipović, Ivan and Nacka-Aleksić, Mirjana and Bufan, Biljana and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2017",
abstract = "The study examined the influence of age, sex and peripubertal gonadectomy on a set of T-cell phenotypic parameters. Rats of both sexes were gonadectomised at the age of 1 month and peripheral blood and spleen T lymphocytes from non-gonadectomised and gonadectomised 3- and 11-month-old rats were examined for the expression of differentiation/activation (CD90/CD45RC) and immunoregulatory markers. Peripheral blood T lymphocytes from non-gonadectomised rats showed age-dependent sexual dimorphisms in (1) total count (lower in female than male 11-month-old rats); (2) CD4+:CD8 + cell ratio (higher in female than male rats of both ages); (3) the proportion of recent thymic emigrants in CD8 + T cells (lower in female than male 3-month-old rats) and (4) the proportions of mature na  lt  ve and memory/activated cells (irrespective of age, the proportion of na  lt  ve cells was higher, whereas that of memory/activated cells was lower in females). Gonadectomy influenced magnitudes or direction of these sex differences. Additionally, sex differences in peripheral blood T-lymphocyte parameters did not fully correspond to those observed in T-splenocyte parameters, suggesting the compartment-specific regulation of the major T-cell subpopulations' and their subsets' composition. Furthermore, there was no sexual dimorphism in the proportion of either CD25 + Foxp3 + cells among CD4 + or CD161+ (NKT) cells within CD8 + T lymphocytes. However, there was gonadal hormone-independent age-associated sexual dimorphism in the proportion of CD161 + cells (NKT cells) in CD8 + T splenocytes. Overall, the study revealed age-dependent variations in sexual dimorphisms in T-cell parameters relevant for immune response efficacy and showed that they are T-cell compartment-specific and partly gonadal hormone-related.",
publisher = "Springer, Dordrecht",
journal = "Molecular and Cellular Biochemistry",
title = "Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy",
volume = "431",
number = "1-2",
pages = "169-185",
doi = "10.1007/s11010-017-2989-x"
}
Arsenović-Ranin, N., Kosec, D., Pilipović, I., Nacka-Aleksić, M., Bufan, B., Stojić-Vukanić, Z.,& Leposavić, G.. (2017). Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 431(1-2), 169-185.
https://doi.org/10.1007/s11010-017-2989-x
Arsenović-Ranin N, Kosec D, Pilipović I, Nacka-Aleksić M, Bufan B, Stojić-Vukanić Z, Leposavić G. Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy. in Molecular and Cellular Biochemistry. 2017;431(1-2):169-185.
doi:10.1007/s11010-017-2989-x .
Arsenović-Ranin, Nevena, Kosec, Duško, Pilipović, Ivan, Nacka-Aleksić, Mirjana, Bufan, Biljana, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy" in Molecular and Cellular Biochemistry, 431, no. 1-2 (2017):169-185,
https://doi.org/10.1007/s11010-017-2989-x . .
9
4
8

Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression

Curuvija, Ivana; Stanojević, Stanislava; Arsenović-Ranin, Nevena; Blagojević, Veljko; Dimitrijević, Mirjana; Vidić-Danković, Biljana; Vujić, Vesna

(Springer/Plenum Publishers, New York, 2017)

TY  - JOUR
AU  - Curuvija, Ivana
AU  - Stanojević, Stanislava
AU  - Arsenović-Ranin, Nevena
AU  - Blagojević, Veljko
AU  - Dimitrijević, Mirjana
AU  - Vidić-Danković, Biljana
AU  - Vujić, Vesna
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3025
AB  - The aim of this study was to examine the influence of sex on age-related changes in phenotype and functional capacity of rat macrophages. The potential role of estradiol as a contributing factor to a sex difference in macrophage function with age was also examined. Thioglycollate-elicited peritoneal macrophages derived from the young (2 months old) and the naturally senescent intact middle-aged (16 months old) male and female rats were tested for cytokine secretion and antimicrobial activity (NO and H2O2 production and myeloperoxidase activity). Serum concentration of estradiol and the expression of estrogen receptor (ER)alpha and ER beta on freshly isolated peritoneal macrophages were also examined. Decreased secretion of IL-1 beta and IL-6 by macrophages from middle-aged compared to the young females was accompanied with the lesser density of macrophage ER alpha expression and the lower systemic level of estradiol, whereas the opposite was true for middle-aged male rats. Macrophages in the middle-aged females, even with the diminished circulating estradiol levels, produce increased amount of IL-6, and comparable amounts of IL-1 beta, TNF-alpha, and NO to that measured in macrophages from the middle-aged males. Age-related changes in macrophage phenotype and the antimicrobial activity were independent of macrophage ER alpha/ER beta expression and estradiol level in both male and female rats. Although our study suggests that the sex difference in the level of circulating estradiol may to some extent contribute to sex difference in macrophage function of middle-aged rats, it also points to more complex hormonal regulation of peritoneal macrophage activity in females.
PB  - Springer/Plenum Publishers, New York
T2  - Inflammation
T1  - Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression
VL  - 40
IS  - 3
SP  - 1087
EP  - 1101
DO  - 10.1007/s10753-017-0551-3
ER  - 
@article{
author = "Curuvija, Ivana and Stanojević, Stanislava and Arsenović-Ranin, Nevena and Blagojević, Veljko and Dimitrijević, Mirjana and Vidić-Danković, Biljana and Vujić, Vesna",
year = "2017",
abstract = "The aim of this study was to examine the influence of sex on age-related changes in phenotype and functional capacity of rat macrophages. The potential role of estradiol as a contributing factor to a sex difference in macrophage function with age was also examined. Thioglycollate-elicited peritoneal macrophages derived from the young (2 months old) and the naturally senescent intact middle-aged (16 months old) male and female rats were tested for cytokine secretion and antimicrobial activity (NO and H2O2 production and myeloperoxidase activity). Serum concentration of estradiol and the expression of estrogen receptor (ER)alpha and ER beta on freshly isolated peritoneal macrophages were also examined. Decreased secretion of IL-1 beta and IL-6 by macrophages from middle-aged compared to the young females was accompanied with the lesser density of macrophage ER alpha expression and the lower systemic level of estradiol, whereas the opposite was true for middle-aged male rats. Macrophages in the middle-aged females, even with the diminished circulating estradiol levels, produce increased amount of IL-6, and comparable amounts of IL-1 beta, TNF-alpha, and NO to that measured in macrophages from the middle-aged males. Age-related changes in macrophage phenotype and the antimicrobial activity were independent of macrophage ER alpha/ER beta expression and estradiol level in both male and female rats. Although our study suggests that the sex difference in the level of circulating estradiol may to some extent contribute to sex difference in macrophage function of middle-aged rats, it also points to more complex hormonal regulation of peritoneal macrophage activity in females.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Inflammation",
title = "Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression",
volume = "40",
number = "3",
pages = "1087-1101",
doi = "10.1007/s10753-017-0551-3"
}
Curuvija, I., Stanojević, S., Arsenović-Ranin, N., Blagojević, V., Dimitrijević, M., Vidić-Danković, B.,& Vujić, V.. (2017). Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression. in Inflammation
Springer/Plenum Publishers, New York., 40(3), 1087-1101.
https://doi.org/10.1007/s10753-017-0551-3
Curuvija I, Stanojević S, Arsenović-Ranin N, Blagojević V, Dimitrijević M, Vidić-Danković B, Vujić V. Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression. in Inflammation. 2017;40(3):1087-1101.
doi:10.1007/s10753-017-0551-3 .
Curuvija, Ivana, Stanojević, Stanislava, Arsenović-Ranin, Nevena, Blagojević, Veljko, Dimitrijević, Mirjana, Vidić-Danković, Biljana, Vujić, Vesna, "Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression" in Inflammation, 40, no. 3 (2017):1087-1101,
https://doi.org/10.1007/s10753-017-0551-3 . .
16
11
14

Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats

Pilipović, Ivan; Vujnović, Ivana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Kosec, Duško; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Elsevier Science BV, Amsterdam, 2016)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Kosec, Duško
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2664
AB  - The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and beta(2)- and alpha(1)-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average beta(2)- and alpha(1)-AR thymocyte surface density changed in the opposite direction with age; the density of beta(2)-AR decreased, whereas that of alpha(1)-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of beta(2)-ARs, but it increased that of alpha(1)-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age-and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats
VL  - 297
SP  - 103
EP  - 116
DO  - 10.1016/j.jneuroim.2016.05.017
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Kosec, Duško and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2016",
abstract = "The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and beta(2)- and alpha(1)-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average beta(2)- and alpha(1)-AR thymocyte surface density changed in the opposite direction with age; the density of beta(2)-AR decreased, whereas that of alpha(1)-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of beta(2)-ARs, but it increased that of alpha(1)-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age-and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats",
volume = "297",
pages = "103-116",
doi = "10.1016/j.jneuroim.2016.05.017"
}
Pilipović, I., Vujnović, I., Arsenović-Ranin, N., Dimitrijević, M., Kosec, D., Stojić-Vukanić, Z.,& Leposavić, G.. (2016). Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 297, 103-116.
https://doi.org/10.1016/j.jneuroim.2016.05.017
Pilipović I, Vujnović I, Arsenović-Ranin N, Dimitrijević M, Kosec D, Stojić-Vukanić Z, Leposavić G. Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. in Journal of Neuroimmunology. 2016;297:103-116.
doi:10.1016/j.jneuroim.2016.05.017 .
Pilipović, Ivan, Vujnović, Ivana, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Kosec, Duško, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats" in Journal of Neuroimmunology, 297 (2016):103-116,
https://doi.org/10.1016/j.jneuroim.2016.05.017 . .
6
4
5

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

(Public Library Science, San Francisco, 2016)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2622
AB  - Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis
VL  - 11
IS  - 11
DO  - 10.1371/journal.pone.0166498
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Petrović, Raisa and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2016",
abstract = "Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis",
volume = "11",
number = "11",
doi = "10.1371/journal.pone.0166498"
}
Stojić-Vukanić, Z., Pilipović, I., Vujnović, I., Nacka-Aleksić, M., Petrović, R., Arsenović-Ranin, N., Dimitrijević, M.,& Leposavić, G.. (2016). GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis. in PLoS One
Public Library Science, San Francisco., 11(11).
https://doi.org/10.1371/journal.pone.0166498
Stojić-Vukanić Z, Pilipović I, Vujnović I, Nacka-Aleksić M, Petrović R, Arsenović-Ranin N, Dimitrijević M, Leposavić G. GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis. in PLoS One. 2016;11(11).
doi:10.1371/journal.pone.0166498 .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Petrović, Raisa, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Leposavić, Gordana, "GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis" in PLoS One, 11, no. 11 (2016),
https://doi.org/10.1371/journal.pone.0166498 . .
1
14
13
14

Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro

Stojić-Vukanić, Zorica; Bufan, Biljana; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Leposavić, Gordana

(Elsevier Science BV, Amsterdam, 2016)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Bufan, Biljana
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2613
AB  - There are little data on modulatory effects of estrogens on rat dendritic cell (DC) responses to inflammatory stimuli, and consequently their ability to activate and polarize CD4+ T lymphocyte-mediated immune responses. Splenic conventional DCs from young female Albino Oxford rats were activated in vitro with LPS (TLR4 agonist) or R848 (TLR7/8 agonist) in the presence and absence of 17 beta-estradiol (E2), and their allostimulatory and CD4+ lymphocyte polarizing ability in mixed leukocyte culture (MLC) were studied. Irrespective of the E2 presence, LPS and R848 up-regulated the expression of MHC II on DCs, so they exhibited enhanced allostimulatory capacity in co-culture with CD4+ lymphocytes. On the other hand, E2 promoted stimulatory action of both TLRs on OX62+ DC IL-23 production, augmented their stimulatory effects on IL-6 and IL-1 beta production, but diminished their enhancing effects on the expression IL-10 and IL-27 by DCs. Consequently, in MLC, OX62+ DCs activated/matured in the co-presence of E2 and either LPS or R848 increased the levels of IL-17, the signature Th17 cell cytoldne, when compared with those activated/matured in the absence of E2. GM-CSF levels were also increased in these MLC. Given that the expression of IL-7 mRNA was diminished in DCs activated/matured in the co presence of E2 and TLR, this increase most likely did not reflect enhanced differentiation of Th cells producing GM-CSF only (Th-GM). Conclusions: E2 augments capacity of LPS- and R848-activated/matured DCs from young rat spleen to induce differentiation of IL-17- and GM-CSF-producing cells.
PB  - Elsevier Science BV, Amsterdam
T2  - International Immunopharmacology
T1  - Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro
VL  - 40
SP  - 244
EP  - 253
DO  - 10.1016/j.intimp.2016.09.001
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Bufan, Biljana and Pilipović, Ivan and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Petrović, Raisa and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2016",
abstract = "There are little data on modulatory effects of estrogens on rat dendritic cell (DC) responses to inflammatory stimuli, and consequently their ability to activate and polarize CD4+ T lymphocyte-mediated immune responses. Splenic conventional DCs from young female Albino Oxford rats were activated in vitro with LPS (TLR4 agonist) or R848 (TLR7/8 agonist) in the presence and absence of 17 beta-estradiol (E2), and their allostimulatory and CD4+ lymphocyte polarizing ability in mixed leukocyte culture (MLC) were studied. Irrespective of the E2 presence, LPS and R848 up-regulated the expression of MHC II on DCs, so they exhibited enhanced allostimulatory capacity in co-culture with CD4+ lymphocytes. On the other hand, E2 promoted stimulatory action of both TLRs on OX62+ DC IL-23 production, augmented their stimulatory effects on IL-6 and IL-1 beta production, but diminished their enhancing effects on the expression IL-10 and IL-27 by DCs. Consequently, in MLC, OX62+ DCs activated/matured in the co-presence of E2 and either LPS or R848 increased the levels of IL-17, the signature Th17 cell cytoldne, when compared with those activated/matured in the absence of E2. GM-CSF levels were also increased in these MLC. Given that the expression of IL-7 mRNA was diminished in DCs activated/matured in the co presence of E2 and TLR, this increase most likely did not reflect enhanced differentiation of Th cells producing GM-CSF only (Th-GM). Conclusions: E2 augments capacity of LPS- and R848-activated/matured DCs from young rat spleen to induce differentiation of IL-17- and GM-CSF-producing cells.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Immunopharmacology",
title = "Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro",
volume = "40",
pages = "244-253",
doi = "10.1016/j.intimp.2016.09.001"
}
Stojić-Vukanić, Z., Bufan, B., Pilipović, I., Vujnović, I., Nacka-Aleksić, M., Petrović, R., Arsenović-Ranin, N.,& Leposavić, G.. (2016). Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro. in International Immunopharmacology
Elsevier Science BV, Amsterdam., 40, 244-253.
https://doi.org/10.1016/j.intimp.2016.09.001
Stojić-Vukanić Z, Bufan B, Pilipović I, Vujnović I, Nacka-Aleksić M, Petrović R, Arsenović-Ranin N, Leposavić G. Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro. in International Immunopharmacology. 2016;40:244-253.
doi:10.1016/j.intimp.2016.09.001 .
Stojić-Vukanić, Zorica, Bufan, Biljana, Pilipović, Ivan, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Petrović, Raisa, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro" in International Immunopharmacology, 40 (2016):244-253,
https://doi.org/10.1016/j.intimp.2016.09.001 . .
3
1
3

Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4

Dimitrijević, Mirjana; Stanojević, Stanislava; Blagojević, Veljko; Curuvija, Ivana; Vujnović, Ivana; Petrović, Raisa; Arsenović-Ranin, Nevena; Vujić, Vesna; Leposavić, Gordana

(Springer, New York, 2016)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Curuvija, Ivana
AU  - Vujnović, Ivana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Vujić, Vesna
AU  - Leposavić, Gordana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2609
AB  - Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18-19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1 beta, IL-6 and IL-10 and downregulated that of TGF-beta was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1 beta and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1 beta and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.
PB  - Springer, New York
T2  - Biogerontology
T1  - Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4
VL  - 17
IS  - 2
SP  - 359
EP  - 371
DO  - 10.1007/s10522-015-9620-x
ER  - 
@article{
author = "Dimitrijević, Mirjana and Stanojević, Stanislava and Blagojević, Veljko and Curuvija, Ivana and Vujnović, Ivana and Petrović, Raisa and Arsenović-Ranin, Nevena and Vujić, Vesna and Leposavić, Gordana",
year = "2016",
abstract = "Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18-19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1 beta, IL-6 and IL-10 and downregulated that of TGF-beta was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1 beta and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1 beta and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4",
volume = "17",
number = "2",
pages = "359-371",
doi = "10.1007/s10522-015-9620-x"
}
Dimitrijević, M., Stanojević, S., Blagojević, V., Curuvija, I., Vujnović, I., Petrović, R., Arsenović-Ranin, N., Vujić, V.,& Leposavić, G.. (2016). Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology
Springer, New York., 17(2), 359-371.
https://doi.org/10.1007/s10522-015-9620-x
Dimitrijević M, Stanojević S, Blagojević V, Curuvija I, Vujnović I, Petrović R, Arsenović-Ranin N, Vujić V, Leposavić G. Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology. 2016;17(2):359-371.
doi:10.1007/s10522-015-9620-x .
Dimitrijević, Mirjana, Stanojević, Stanislava, Blagojević, Veljko, Curuvija, Ivana, Vujnović, Ivana, Petrović, Raisa, Arsenović-Ranin, Nevena, Vujić, Vesna, Leposavić, Gordana, "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4" in Biogerontology, 17, no. 2 (2016):359-371,
https://doi.org/10.1007/s10522-015-9620-x . .
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Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation

Bufan, Biljana; Stojić-Vukanić, Zorica; Đikić, Jasmina; Kosec, Duško; Pilipović, Ivan; Nacka-Aleksić, Mirjana; Arsenović-Ranin, Nevena; Leposavić, Gordana

(Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd, 2015)

TY  - JOUR
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Đikić, Jasmina
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Nacka-Aleksić, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2416
AB  - The study was undertaken considering: i) that relative proportion of distinct subsets of splenic dendritic cells (DCs) is strain-specific and predictive for the susceptibility to autoimmune diseases; ii) age-related changes in endocytic, allostimulatory and polarizing capacity of splenic OX62+ DCs from Albino Oxford rats (relatively resistant to Th1/Th17-mediated diseases) and iii) strain specificities in age-related changes of mouse DCs. To ascertain whether there are strain specificities in age-related rat DC changes, we examined the influence of aging on OX62+ DCs from Dark Agouti (DA) rats prone to Th1/Th17-mediated autoimmune diseases. The study provided additional evidence that the predominance of CD4-cells within OX62+ DCs from young adult rats correlates with their susceptibility to Th1/Th17-mediated diseases. Consistently, lipopolysaccharide (LPS)-matured DCs from 3-month-old (young) rats exhibited Th1 driving force when co-cultured with allogeneic CD4+ T cells. This most likely reflected enhanced TNF-alpha and iNOS expression. Comparing with young rats, OX62+ DCs from 26-month-old (aged) rats showed: i) diminished endocytic capacity; ii) impaired ability to mature in vitro upon LPS stimulation (as indicated by lower MHC II, CD86 and CD40 surface expression), which is consistent with the increase in their IL-10 production, and iii) diminished allostimulatory capacity and loss of Th1-driving capacity in the mixed lymphocyte reaction. The latter, probably, reflected greater IL-10 production by LPS-stimulated DC from aged rats, as well as lower CD40 density on their surface. Overall, our findings suggest that aging might affect DA rat capability to mount an efficient Th1 immune response, and consequently susceptibility to Th1/Th17-mediated pathology.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation
VL  - 65
IS  - 1
SP  - 30
EP  - 55
DO  - 10.1515/acve-2015-0003
ER  - 
@article{
author = "Bufan, Biljana and Stojić-Vukanić, Zorica and Đikić, Jasmina and Kosec, Duško and Pilipović, Ivan and Nacka-Aleksić, Mirjana and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2015",
abstract = "The study was undertaken considering: i) that relative proportion of distinct subsets of splenic dendritic cells (DCs) is strain-specific and predictive for the susceptibility to autoimmune diseases; ii) age-related changes in endocytic, allostimulatory and polarizing capacity of splenic OX62+ DCs from Albino Oxford rats (relatively resistant to Th1/Th17-mediated diseases) and iii) strain specificities in age-related changes of mouse DCs. To ascertain whether there are strain specificities in age-related rat DC changes, we examined the influence of aging on OX62+ DCs from Dark Agouti (DA) rats prone to Th1/Th17-mediated autoimmune diseases. The study provided additional evidence that the predominance of CD4-cells within OX62+ DCs from young adult rats correlates with their susceptibility to Th1/Th17-mediated diseases. Consistently, lipopolysaccharide (LPS)-matured DCs from 3-month-old (young) rats exhibited Th1 driving force when co-cultured with allogeneic CD4+ T cells. This most likely reflected enhanced TNF-alpha and iNOS expression. Comparing with young rats, OX62+ DCs from 26-month-old (aged) rats showed: i) diminished endocytic capacity; ii) impaired ability to mature in vitro upon LPS stimulation (as indicated by lower MHC II, CD86 and CD40 surface expression), which is consistent with the increase in their IL-10 production, and iii) diminished allostimulatory capacity and loss of Th1-driving capacity in the mixed lymphocyte reaction. The latter, probably, reflected greater IL-10 production by LPS-stimulated DC from aged rats, as well as lower CD40 density on their surface. Overall, our findings suggest that aging might affect DA rat capability to mount an efficient Th1 immune response, and consequently susceptibility to Th1/Th17-mediated pathology.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation",
volume = "65",
number = "1",
pages = "30-55",
doi = "10.1515/acve-2015-0003"
}
Bufan, B., Stojić-Vukanić, Z., Đikić, J., Kosec, D., Pilipović, I., Nacka-Aleksić, M., Arsenović-Ranin, N.,& Leposavić, G.. (2015). Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 65(1), 30-55.
https://doi.org/10.1515/acve-2015-0003
Bufan B, Stojić-Vukanić Z, Đikić J, Kosec D, Pilipović I, Nacka-Aleksić M, Arsenović-Ranin N, Leposavić G. Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation. in Acta veterinaria. 2015;65(1):30-55.
doi:10.1515/acve-2015-0003 .
Bufan, Biljana, Stojić-Vukanić, Zorica, Đikić, Jasmina, Kosec, Duško, Pilipović, Ivan, Nacka-Aleksić, Mirjana, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Aging impairs endocytic capacity of splenic dendritic cells from Dark Agouti rats and alters their response to TLR4 stimulation" in Acta veterinaria, 65, no. 1 (2015):30-55,
https://doi.org/10.1515/acve-2015-0003 . .
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Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis

Đikić, Jasmina; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Kosec, Duško; Arsenović-Ranin, Nevena; Stojić-Vukanić, Zorica; Dimitrijević, Mirjana; Leposavić, Gordana

(Elsevier Science BV, Amsterdam, 2015)

TY  - JOUR
AU  - Đikić, Jasmina
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2413
AB  - The study was undertaken considering age-related changes in susceptibility to experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in pathogenesis of this disease. The phenotypic and functional characteristics of T splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in complete Freund's adjuvant The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging. To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3 and CD4+CD40L+ cells, progressively increased with aging. This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3 + cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system. In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones. Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats. In addition, in control, as well as in ConA-and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-gamma concentrations were greater than in corresponding cultures from young rats. This most likely reflected increased abundance of IFN-gamma-producing cells in splenocyte cultures from aged compared with young rats. The diminished CD4+ cell proliferation in response to ConA and MBP in splenocyte cultures from aged compared with young rats could be, at least partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats. Thus, the study suggests that age-associated changes leading to entrapping of activated CD4+ cells in the spleen could contribute to the restriction in development of EAE in aged rats.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis
VL  - 278
SP  - 123
EP  - 135
DO  - 10.1016/j.jneuroim.2014.12.014
ER  - 
@article{
author = "Đikić, Jasmina and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Kosec, Duško and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2015",
abstract = "The study was undertaken considering age-related changes in susceptibility to experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in pathogenesis of this disease. The phenotypic and functional characteristics of T splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in complete Freund's adjuvant The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging. To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3 and CD4+CD40L+ cells, progressively increased with aging. This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3 + cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system. In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones. Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats. In addition, in control, as well as in ConA-and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-gamma concentrations were greater than in corresponding cultures from young rats. This most likely reflected increased abundance of IFN-gamma-producing cells in splenocyte cultures from aged compared with young rats. The diminished CD4+ cell proliferation in response to ConA and MBP in splenocyte cultures from aged compared with young rats could be, at least partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats. Thus, the study suggests that age-associated changes leading to entrapping of activated CD4+ cells in the spleen could contribute to the restriction in development of EAE in aged rats.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis",
volume = "278",
pages = "123-135",
doi = "10.1016/j.jneuroim.2014.12.014"
}
Đikić, J., Nacka-Aleksić, M., Pilipović, I., Kosec, D., Arsenović-Ranin, N., Stojić-Vukanić, Z., Dimitrijević, M.,& Leposavić, G.. (2015). Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 278, 123-135.
https://doi.org/10.1016/j.jneuroim.2014.12.014
Đikić J, Nacka-Aleksić M, Pilipović I, Kosec D, Arsenović-Ranin N, Stojić-Vukanić Z, Dimitrijević M, Leposavić G. Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2015;278:123-135.
doi:10.1016/j.jneuroim.2014.12.014 .
Đikić, Jasmina, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Kosec, Duško, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Leposavić, Gordana, "Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 278 (2015):123-135,
https://doi.org/10.1016/j.jneuroim.2014.12.014 . .
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