The Polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper Type 1 and type 2 cells

Damon J. Tumes, Atsushi Onodera, Akane Suzuki, Kenta Shinoda, Yusuke Endo, Chiaki Iwamura, Hiroyuki Hosokawa, Haruhiko Koseki, Koji Tokoyoda, Yutaka Suzuki, Shinichiro Motohashi, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

181 Citations (Scopus)

Abstract

After antigen encounter by CD4+ Tcells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial trimethylation at lysine 27 of histone 3 (H3K27me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-γ expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. Invivo, loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells. This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4+ Tcells.

Original languageEnglish
Pages (from-to)819-832
Number of pages14
JournalImmunity
Volume39
Issue number5
DOIs
Publication statusPublished or Issued - 14 Nov 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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