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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

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


  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • IL1R1 protein, mouse
  • Interleukin-6
  • MicroRNAs
  • Mirn182 microRNA, mouse
  • Mirn183 microRNA, mouse
  • Mirn96 microRNA, mouse
  • Receptors, Interleukin-1 Type I
  • STAT3 Transcription Factor
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases