Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study
| Autor: | Bojana Simovic Markovic, Zana Dolicanin, Valentin Djonov, Ilija Jeftic, Marina Gazdic, Neda Milosavljevic, Miodrag L. Lukic, Nebojsa Arsenijevic, Vladislav Volarevic, Nemanja Jovicic, Jasmin Nurkovic, Aleksandar Arsenijevic |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Pathology medicine.medical_specialty CCL4 Mesenchymal Stem Cell Transplantation Flow cytometry 03 medical and health sciences chemistry.chemical_compound Fibrosis Paracrine Communication medicine Animals Indoleamine-Pyrrole 2 3 -Dioxygenase 610 Medicine & health Sirius Red Carbon Tetrachloride Transplantation medicine.diagnostic_test business.industry Mesenchymal stem cell Interleukin-17 FOXP3 Mesenchymal Stem Cells medicine.disease Mice Inbred C57BL 030104 developmental biology chemistry Cancer research Th17 Cells Interleukin 17 business Kynurenine |
| Zdroj: | Transplant international : official journal of the European Society for Organ Transplantation. 31(1) |
| ISSN: | 1432-2277 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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