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

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. The histone demethylase Jmjd3 is involved in many biological processes. Here, the authors generate T cell-specific Jmjd3-deficient mice and show that Jmjd3 has a role in T-cell function and in the differentiation and interconversion of T-cell subsets in the intestine.