miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression

Immunity. 2014 Jun 19;40(6):865-79. doi: 10.1016/j.immuni.2014.03.014. Epub 2014 May 22.


Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism
  • Animals
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Chromatin / genetics
  • Cytokines / genetics*
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / immunology*
  • Polycomb Repressive Complex 2 / metabolism
  • Protein Binding
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology*


  • Activating Transcription Factor 3
  • Chromatin
  • Cytokines
  • JARID2 protein, human
  • Jarid2 protein, mouse
  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE37228
  • GEO/GSE47528