期刊
IMMUNOLOGIC RESEARCH
卷 61, 期 3, 页码 219-229出版社
HUMANA PRESS INC
DOI: 10.1007/s12026-014-8612-2
关键词
MSC; Th17; IFN-gamma; SOCS3
类别
资金
- National Key Scientific Program of China [2011CB964901]
- Program for International S&T Cooperation Projects of China [2013DFG30680]
- National Natural Science Foundation of China [81370879, 81370466]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2014ZX09101042]
- Key Program for Beijing Municipal Natural Science Foundation [7141006]
Mesenchymal stem cells (MSCs) are immunoregulatory, and the administration of them has been shown to ameliorate inflammation caused by Th17 cells. However, the mechanisms that contribute to MSC regulation on Th17 cell development are unclear. Here, we found that MSCs could inhibit Th17 cell differentiation through the activation of suppressors of cytokine signaling 3 (SOCS3) when coculture of MSCs and CD4(+)CD25(low)CD44(low)CD62L(high) T cells. Further analysis demonstrated that the inhibitory action was mediated via interferon gamma (IFN-gamma), which activated signal transducer and activator of transcription-1 (STAT1) to enhance the expression of SOCS3, leading to STAT3 inhibition. Moreover, stable and reciprocal changes in H3K4me3 and H3K27me3 at the promoters of STAT1, STAT3 and ROR gamma t determined the fate of Th17 cells. These results demonstrate that MSCs may inhibit Th17 differentiation via IFN-gamma that activates SOCS3 leading to immunomodulatory effects, suggesting a possible mechanism by which MSCs could act as a cellular approach to attenuate the clinical and pathological manifestations of some autoimmune diseases.
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