Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation

Nat Commun. 2014 Dec 22;5:5780. doi: 10.1038/ncomms6780.

Abstract

Epigenetic factors have been implicated in the regulation of CD4(+) T-cell differentiation. Jmjd3 plays a role in many biological processes, but its in vivo function in T-cell differentiation remains unknown. Here we report that Jmjd3 ablation promotes CD4(+) T-cell differentiation into Th2 and Th17 cells in the small intestine and colon, and inhibits T-cell differentiation into Th1 cells under different cytokine-polarizing conditions and in a Th1-dependent colitis model. Jmjd3 deficiency also restrains the plasticity of the conversion of Th2, Th17 or Treg cells to Th1 cells. The skewing of T-cell differentiation is concomitant with changes in the expression of key transcription factors and cytokines. H3K27me3 and H3K4me3 levels in Jmjd3-deficient cells are correlated with altered gene expression through interactions with specific transcription factors. Our results identify Jmjd3 as an epigenetic factor in T-cell differentiation via changes in histone methylation and target gene expression.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / enzymology*
  • Cell Differentiation*
  • Cells, Cultured
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th1 Cells / cytology
  • Th1 Cells / enzymology
  • Th17 Cells / cytology
  • Th17 Cells / enzymology
  • Th2 Cells / cytology
  • Th2 Cells / enzymology

Substances

  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, mouse