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 . .