YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity

被引：49

作者：

Hwang, Soo Seok ^{[1
,2
,3
]}

Jang, Sung Woong ^{[1
]}

Kim, Min Kyung ^{[1
]}

Kim, Lark Kyun ^{[2
,3
]}

Kim, Bong-Sung ^{[4
,5
,6
]}

Kim, Hyeong Su ^{[1
]}

Kim, Kiwan ^{[1
]}

Lee, Wonyong ^{[1
]}

Flavell, Richard A. ^{[2
,3
]}

Lee, Gap Ryol ^{[1
]}

机构：

[1] Sogang Univ, Dept Life Sci, 35 Baekbeom Ro, Seoul 121742, South Korea

[2] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Dept Rheumatol, 333 Cedar St, New Haven, CT 06520 USA

[5] Rhein Westfal TH Aachen, Hand Surg Burn Ctr, Dept Plast & Reconstruct Surg, Templergraben 55, D-52062 Aachen, Germany

[6] Rhein Westfal TH Aachen, Inst Biochem & Mol Cell Biol, Templergraben 55, D-52062 Aachen, Germany

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

新加坡国家研究基金会;

关键词：

TRANSCRIPTION FACTOR FOXP3; TARGET GENES; MECHANISMS; PLASTICITY; YIN-YANG-1; PROTEIN; IDENTIFICATION; GENERATION; OCCUPANCY; PROGRAMS;

D O I：

10.1038/ncomms10789

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：

Regulatory T (T-reg) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T-reg-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T-reg cells than T-conv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of T-reg cells. YY1 is increased in T-reg cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T-reg cells by blocking Foxp3.

引用

页数：15

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