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dc.creatorDimitrijević, Mirjana
dc.creatorArsenović-Ranin, Nevena
dc.creatorKosec, Duško
dc.creatorBufan, Biljana
dc.creatorNacka-Aleksić, Mirjana
dc.creatorPilipović, Ivan
dc.creatorLeposavić, Gordana
dc.date.accessioned2019-09-02T12:09:49Z
dc.date.available2019-09-02T12:09:49Z
dc.date.issued2019
dc.identifier.issn0889-1591
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3295
dc.description.abstractCollagen 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.en
dc.publisherAcademic Press Inc Elsevier Science, San Diego
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsrestrictedAccess
dc.sourceBrain Behavior and Immunity
dc.subjectCollagen-induced arthritisen
dc.subjectSex differencesen
dc.subjectTh17/Treg axis plasticityen
dc.subjectIL-35en
dc.subjectBregsen
dc.titleSexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritisen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПилиповић, Иван; Aрсеновић-Ранин, Невена; Димитријевић, Мирјана; Косец, Душко; Лепосавић, Гордана; Нацка-Aлексић, Мирјана; Буфан, Биљана;
dc.citation.volume76
dc.citation.spage198
dc.citation.epage214
dc.citation.other76: 198-214
dc.citation.rankaM21
dc.identifier.wos000458089300021
dc.identifier.doi10.1016/j.bbi.2018.11.311
dc.identifier.pmid30476564
dc.identifier.scopus2-s2.0-85057290696
dc.identifier.rcubconv_4314
dc.type.versionpublishedVersion


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