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dc.contributor.authorMilosavljevic N.-
dc.contributor.authorGazdic, Marina-
dc.contributor.authorSimovic Markovic, Bojana-
dc.contributor.authorArsenijevic A.-
dc.contributor.authorNurkovic J.https-
dc.contributor.authorDolicanin Z.-
dc.contributor.authorJovicic, Nemanja-
dc.contributor.authorJeftic, Ilija-
dc.contributor.authorDjonov V.-
dc.contributor.authorArsenijevic, Nebojsa-
dc.contributor.authorLukic, Miodrag-
dc.contributor.authorVolarevic, Vladislav-
dc.description.abstract© 2017 Steunstichting ESOT This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1 μl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 106), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl4 and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl4-induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4+IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+FoxP3+IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis.-
dc.relation.ispartofTransplant International-
dc.titleMesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells – an experimental study-
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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