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Immunity. 2016 Jun 21;44(6):1284-98. doi: 10.1016/j.immuni.2016.05.015.

The MicroRNA-183-96-182 Cluster Promotes T Helper 17 Cell Pathogenicity by Negatively Regulating Transcription Factor Foxo1 Expression.

Author information

1
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
2
Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA.
4
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, People's Republic of China.
5
Department of Ophthalmology, Kresge Eye Institute, Detroit, MI 48201, USA; Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48202, USA.
6
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA.
7
Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: cxiao@scripps.edu.
8
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, People's Republic of China. Electronic address: chendong@tsinghua.edu.cn.

Abstract

T helper 17 (Th17) cells are key players in autoimmune diseases. However, the roles of non-coding RNAs in Th17 cell development and function are largely unknown. We found that deletion of the endoribonuclease-encoding Dicer1 specifically in Th17 cells protected mice from experimental autoimmune encephalomyelitis. We found that the Dicer1-regulated microRNA (miR)-183-96-182 cluster (miR-183C) was highly expressed in Th17 cells and was induced by cytokine IL-6-STAT3 signaling. miR-183C expression enhanced pathogenic cytokine production from Th17 cells during their development and promoted autoimmunity. Mechanistically, miR-183C in Th17 cells directly repressed expression of the transcription factor Foxo1. Foxo1 negatively regulated the pathogenicity of Th17 cells in part by inhibiting expression of cytokine receptor IL-1R1. These findings indicate that the miR-183C drives Th17 pathogenicity in autoimmune diseases via inhibition of Foxo1 and present promising therapeutic targets.

PMID:
27332731
PMCID:
PMC4918454
DOI:
10.1016/j.immuni.2016.05.015
[Indexed for MEDLINE]
Free PMC Article

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