Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity
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 f...
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doaj-db6f6fd7426d4c6bb86a1e438cf9217c2020-11-24T23:54:38ZengElsevierCell Reports2211-12472017-10-0121119520710.1016/j.celrep.2017.09.021Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in AutoimmunityByung-Seok Kim0Huiping Lu1Kenji Ichiyama2Xiang Chen3Yi-Bing Zhang4Nipun A. Mistry5Kentaro Tanaka6Young-hee Lee7Roza Nurieva8Li Zhang9Xuexian Yang10Yeonseok Chung11Wei Jin12Seon Hee Chang13Chen Dong14Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USAInstitute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, ChinaDepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USAState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaDepartment of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Environmental Health, University of Cincinnati, Cincinnati, OH 45219, USADepartment of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USALaboratory of Immune Regulation, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaInstitute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, ChinaDepartment of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USAInstitute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, ChinaTh17 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.http://www.sciencedirect.com/science/article/pii/S2211124717312962TregRORγtFoxp3autoimmunityIL-17Tr17 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Byung-Seok Kim Huiping Lu Kenji Ichiyama Xiang Chen Yi-Bing Zhang Nipun A. Mistry Kentaro Tanaka Young-hee Lee Roza Nurieva Li Zhang Xuexian Yang Yeonseok Chung Wei Jin Seon Hee Chang Chen Dong |
spellingShingle |
Byung-Seok Kim Huiping Lu Kenji Ichiyama Xiang Chen Yi-Bing Zhang Nipun A. Mistry Kentaro Tanaka Young-hee Lee Roza Nurieva Li Zhang Xuexian Yang Yeonseok Chung Wei Jin Seon Hee Chang Chen Dong Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity Cell Reports Treg RORγt Foxp3 autoimmunity IL-17 Tr17 |
author_facet |
Byung-Seok Kim Huiping Lu Kenji Ichiyama Xiang Chen Yi-Bing Zhang Nipun A. Mistry Kentaro Tanaka Young-hee Lee Roza Nurieva Li Zhang Xuexian Yang Yeonseok Chung Wei Jin Seon Hee Chang Chen Dong |
author_sort |
Byung-Seok Kim |
title |
Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity |
title_short |
Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity |
title_full |
Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity |
title_fullStr |
Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity |
title_full_unstemmed |
Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity |
title_sort |
generation of rorγt+ antigen-specific t regulatory 17 cells from foxp3+ precursors in autoimmunity |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-10-01 |
description |
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. |
topic |
Treg RORγt Foxp3 autoimmunity IL-17 Tr17 |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717312962 |
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