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dc.creatorStojić-Vukanić, Zorica
dc.creatorPilipović, Ivan
dc.creatorVujnović, Ivana
dc.creatorNacka-Aleksić, Mirjana
dc.creatorPetrović, Raisa
dc.creatorArsenović-Ranin, Nevena
dc.creatorDimitrijević, Mirjana
dc.creatorLeposavić, Gordana
dc.date.accessioned2019-09-02T11:52:51Z
dc.date.available2019-09-02T11:52:51Z
dc.date.issued2016
dc.identifier.issn1932-6203
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2622
dc.description.abstractGiven 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.en
dc.publisherPublic Library Science, San Francisco
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsopenAccess
dc.sourcePLoS One
dc.titleGM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitisen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractНацка-Aлексић, Мирјана; Пилиповић, Иван; Вујновић, Ивана; Aрсеновић-Ранин, Невена; Лепосавић, Гордана; Димитријевић, Мирјана; Петровић, Раиса; Стојић-Вуканић, Зорица;
dc.citation.volume11
dc.citation.issue11
dc.citation.other11(11): -
dc.citation.rankM21
dc.identifier.wos000387725000131
dc.identifier.doi10.1371/journal.pone.0166498
dc.identifier.pmid27832210
dc.identifier.scopus2-s2.0-84994761805
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1300/2620.pdf
dc.identifier.rcubconv_3698
dc.type.versionpublishedVersion


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