The Polycomb Protein Ezh2 Regulates Differentiation and Plasticity of CD4+ T Helper Type 1 and Type 2 Cells

被引：284

作者：

Tumes, Damon J. ^{[1
]}

Onodera, Atsushi ^{[1
]}

Suzuki, Akane ^{[1
]}

Shinoda, Kenta ^{[1
]}

Endo, Yusuke ^{[1
]}

Iwamura, Chiaki ^{[1
]}

Hosokawa, Hiroyuki ^{[1
]}

Koseki, Haruhiko ^{[2
]}

Tokoyoda, Koji ^{[1
]}

Suzuki, Yutaka ^{[3
]}

Motohashi, Shinichiro ^{[4
]}

Nakayama, Toshinori ^{[1
,5
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, Chiba 2608670, Japan

[2] RIKEN Ctr Integrat Med Sci IMS RCAI, Lab Dev Genet, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[3] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Kashiwa, Chiba 2778562, Japan

[4] Chiba Univ, Grad Sch Med, Dept Med Immunol, Chuo Ku, Chiba 2608670, Japan

[5] JST, CREST, Chuo Ku, Chiba 2608670, Japan

来源：

IMMUNITY | 2013年 / 39卷 / 05期

关键词：

IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; GENE-EXPRESSION; TH1; BET; METHYLATION; GATA-3; MAINTENANCE; REPRESSION;

D O I：

10.1016/j.immuni.2013.09.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

After antigen encounter by CD4(+) T cells, 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-gamma and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-gamma expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. In vivo, 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(+) T cells.

引用

页码：819 / 832

页数：14

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