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

Qingtian Li, Jia Zou, Mingjun Wang, Xilai Ding, Iouri Chepelev, Xikun Zhou, Wei Zhao, Gang Wei, Jun Cui, Keji Zhao, Helen Y. Wang, Rong Fu Wang

Research output: Contribution to journalArticle

70 Scopus citations

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.

Original languageEnglish (US)
Article number5780
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Critical role of histone demethylase Jmjd3 in the regulation of CD4 <sup>+</sup> T-cell differentiation'. Together they form a unique fingerprint.

Cite this