Eos Mediates Foxp3-Dependent Gene Silencing in CD4+ Regulatory T Cells

被引：254

作者：

Pan, Fan ^{[1
]}

Yu, Hong ^{[1
]}

Dang, Eric V. ^{[1
]}

Barbi, Joseph ^{[1
]}

Pan, Xiaoyu ^{[1
]}

Grosso, Joseph F. ^{[1
]}

Jinasena, Dinili ^{[1
]}

Sharma, Sudarshana M. ^{[2
,3
]}

McCadden, Erin M. ^{[1
]}

Getnet, Derese ^{[1
]}

Drake, Charles G. ^{[1
]}

Liu, Jun O. ^{[4
]}

Ostrowski, Michael C. ^{[2
,3
]}

Pardoll, Drew M. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Immunol & Hematopoiesis Div, Baltimore, MD 21231 USA

[2] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA

[3] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

SCIENCE | 2009年 / 325卷 / 5944期

关键词：

INTESTINAL INFLAMMATION; IN-VIVO; FOXP3; DEMETHYLATION; TRANSCRIPTION; COREPRESSORS; IKAROS;

D O I：

10.1126/science.1176077

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CD4(+) regulatory T cells (T-regs) maintain immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses. The core genetic program of T-regs and their ability to suppress pathologic immune responses depends on the transcription factor Foxp3. Despite progress in understanding mechanisms of Foxp3-dependent gene activation, the molecular mechanism of Foxp3-dependent gene repression remains largely unknown. We identified Eos, a zinc-finger transcription factor of the Ikaros family, as a critical mediator of Foxp3-dependent gene silencing in T-regs. Eos interacts directly with Foxp3 and induces chromatin modifications that result in gene silencing in T-regs. Silencing of Eos in T-regs abrogates their ability to suppress immune responses and endows them with partial effector function, thus demonstrating the critical role that Eos plays in T-reg programming.

引用

页码：1142 / 1146

页数：5

共 24 条

[1] Foxp3 interacts with nuclear factor of activated T cells and NF-κB to repress cytokine gene expression and effector functions of T helper cells [J].