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Cell Rep. 2017 Oct 3;21(1):195-207. doi: 10.1016/j.celrep.2017.09.021.

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

Author information

1
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA; Laboratory of Immune Regulation, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
2
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
3
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA.
4
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
5
Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77054, USA.
6
Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45219, USA.
7
Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA.
8
Laboratory of Immune Regulation, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
9
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: shchang@mdanderson.org.
10
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: chendong@tsinghua.edu.cn.

Abstract

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.

KEYWORDS:

Foxp3; IL-17; RORγt; Tr17; Treg; autoimmunity

PMID:
28978473
PMCID:
PMC5716359
DOI:
10.1016/j.celrep.2017.09.021
[Indexed for MEDLINE]
Free PMC Article

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