Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion

被引:113
作者
Qu, Xuebin [1 ,2 ,3 ]
Liu, Xingxia [1 ,2 ,3 ]
Cheng, Kai [1 ,2 ,3 ]
Yang, Rongcun [4 ]
Zhao, Robert C. H. [1 ,2 ,3 ]
机构
[1] Chinese Acad Med Sci, Ctr Excellence Tissue Engn, Inst Basic Med Sci, Beijing 100005, Peoples R China
[2] Chinese Acad Med Sci, Ctr Excellence Tissue Engn, Sch Basic Med, Beijing 100005, Peoples R China
[3] Peking Union Med Coll, Beijing 100005, Peoples R China
[4] Nankai Univ, Sch Med, Dept Immunol, Tianjin 300071, Peoples R China
基金
中国国家自然科学基金;
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; MARROW STROMAL CELLS; REGULATORY T-CELLS; LYMPHOCYTE-PROLIFERATION; IFN-GAMMA; ROR-GAMMA; TGF-BETA; INTERLEUKIN-10; INFLAMMATION;
D O I
10.1016/j.exphem.2012.05.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent findings indicate that mesenchymal stem cells (MSCs) may act as a regulator of Th17 cell differentiation, however, the underlying mechanism is still under debate. To investigate the underlying mechanisms of MSCs' regulatory effect, mouse bone marrow-derived MSCs were cocultured with mouse CD4(+)CD25(low)CD44(low)CD62L(high) T cells in vitro, and the proportion of induced Th17 cells, cytokines secretion, and transcription factors expression were examined by flow cytometry, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and Western blotting. For the first time, our results showed that bone marrow-derived MSCs were able to inhibit Th17 cell differentiation via interleukin (IL)-10 secretion as the Th17 cell proportion was significantly regained when IL-10 was neutralized, or expression of IL-10 by bane marrow-derived MSCs was downregulated by RNA interference technique. Furthermore, IL-10 may suppress expression of Ror gamma t, the key transcription factor for Th17 cells, both by activating suppressor of cytokine signaling 3 through signal transducers and activators of transcription 5 phosphorylation, and decreasing signal transducers and activators of transcription 3 binding, which is at the promoter of Ror gamma t. Thus, our results demonstrate the inhibitory effect of MSCs on Th17 cells differentiation, and suggest increased IL-10 secretion might be the key factor. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:761 / 770
页数:10
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