Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level
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2015
Authors
Nacka-Aleksić, MirjanaĐikić, Jasmina
Pilipović, Ivan
Stojić-Vukanić, Zorica
Kosec, Duško
Bufan, Biljana
Arsenović-Ranin, Nevena
Dimitrijević, Mirjana
Leposavić, Gordana
Article (Published version)
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Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamm...a+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE.
Source:
Brain Behavior and Immunity, 2015, 49, 101-118Publisher:
- Academic Press Inc Elsevier Science, San Diego
Funding / projects:
- Immune system plasticity during aging: Immunomodulatory capacity of oestrogens (RS-MESTD-Basic Research (BR or ON)-175050)
DOI: 10.1016/j.bbi.2015.04.017
ISSN: 0889-1591
PubMed: 25944279
WoS: 000361257900014
Scopus: 2-s2.0-84940598922
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PharmacyTY - JOUR AU - Nacka-Aleksić, Mirjana AU - Đikić, Jasmina AU - Pilipović, Ivan AU - Stojić-Vukanić, Zorica AU - Kosec, Duško AU - Bufan, Biljana AU - Arsenović-Ranin, Nevena AU - Dimitrijević, Mirjana AU - Leposavić, Gordana PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2348 AB - Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. PB - Academic Press Inc Elsevier Science, San Diego T2 - Brain Behavior and Immunity T1 - Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level VL - 49 SP - 101 EP - 118 DO - 10.1016/j.bbi.2015.04.017 ER -
@article{ author = "Nacka-Aleksić, Mirjana and Đikić, Jasmina and Pilipović, Ivan and Stojić-Vukanić, Zorica and Kosec, Duško and Bufan, Biljana and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Leposavić, Gordana", year = "2015", abstract = "Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE.", publisher = "Academic Press Inc Elsevier Science, San Diego", journal = "Brain Behavior and Immunity", title = "Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level", volume = "49", pages = "101-118", doi = "10.1016/j.bbi.2015.04.017" }
Nacka-Aleksić, M., Đikić, J., Pilipović, I., Stojić-Vukanić, Z., Kosec, D., Bufan, B., Arsenović-Ranin, N., Dimitrijević, M.,& Leposavić, G.. (2015). Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level. in Brain Behavior and Immunity Academic Press Inc Elsevier Science, San Diego., 49, 101-118. https://doi.org/10.1016/j.bbi.2015.04.017
Nacka-Aleksić M, Đikić J, Pilipović I, Stojić-Vukanić Z, Kosec D, Bufan B, Arsenović-Ranin N, Dimitrijević M, Leposavić G. Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level. in Brain Behavior and Immunity. 2015;49:101-118. doi:10.1016/j.bbi.2015.04.017 .
Nacka-Aleksić, Mirjana, Đikić, Jasmina, Pilipović, Ivan, Stojić-Vukanić, Zorica, Kosec, Duško, Bufan, Biljana, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Leposavić, Gordana, "Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level" in Brain Behavior and Immunity, 49 (2015):101-118, https://doi.org/10.1016/j.bbi.2015.04.017 . .