Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity

Cell Reports

Nipun A. Mistry¹  Li Zhang²  Byung-Seok Kim³  Kentaro Tanaka³  Xiang Chen³  Kenji Ichiyama³  Seon Hee Chang³  Young-hee Lee³  Roza Nurieva³  Xuexian Yang⁴  Chen Dong⁵  Wei Jin⁵  Huiping Lu⁵  Yeonseok Chung⁶  Yi-Bing Zhang⁷ 

[1] Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77054, USA;Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45219, USA;Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA;Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA;Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China;Laboratory of Immune Regulation, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea;State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;

关键词: Treg;    RORγt;    Foxp3;    autoimmunity;    IL-17;    Tr17;   

DOI  :  10.1016/j.celrep.2017.09.021

来源: DOAJ

【 摘 要 】

Th17 cells are potent mediators in autoimmune diseases, and RORγt is required for their development. Recent studies have shown that RORγt+ Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORγt+ Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORγt+ Treg cells in their transcriptomes, peripheral RORγt+ Treg cells were derived from Foxp3+ thymic Treg cells in an antigen-specific manner. Development of these RORγt+ Treg cells, coined T regulatory 17 (Tr17) cells, depended on IL-6/Stat3 signaling. Tr17 cells showed suppressive activity against antigen-specific effector T cells in vitro. In addition, Tr17 cells efficiently inhibited myelin-specific Th17-cell-mediated CNS auto-inflammation in a passive EAE model. Collectively, our study demonstrates that Tr17 cells are effector Treg cells that potentially restrict autoimmunity.

【 授权许可】

Unknown