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

Q Li, J Zou, M Wang, X Ding, I Chepelev, X Zhou… - Nature …, 2014 - nature.com
Q Li, J Zou, M Wang, X Ding, I Chepelev, X Zhou, W Zhao, G Wei, J Cui, K Zhao, HY Wang…
Nature communications, 2014nature.com
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 …
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.
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