Title

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

Document Type

Journal Article

Publication Date

6-21-2016

Journal

Immunity

Volume

44

Issue

6

Inclusive Pages

1284-98

DOI

10.1016/j.immuni.2016.05.015

Keywords

Animals; Cells, Cultured; DEAD-box RNA Helicases; Encephalomyelitis, Autoimmune, Experimental; Forkhead Box Protein O1; Humans; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Multiple Sclerosis; Receptors, Interleukin-1 Type I; Ribonuclease III; STAT3 Transcription Factor; Th17 Cells

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.

Comments

This is an open access PubMed Central article.

Peer Reviewed

1

Open Access

1