T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt

被引：305

作者：

Lazarevic, Vanja ^{[1
]}

Chen, Xi ^{[1
]}

Shim, Jae-Hyuck ^{[1
]}

Hwang, Eun-Sook ^{[2
]}

Jang, Eunjung ^{[2
]}

Bolm, Alexandra N. ^{[1
]}

Oukka, Mohamed ^{[3
]}

Kuchroo, Vijay K. ^{[4
]}

Glimcher, Laurie H. ^{[1
,5
,6
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[2] Ewha Womans Univ, Coll Pharm, Div Life & Pharmaceut Sci, Seoul, South Korea

[3] Seattle Childrens Res Inst, Dept Pediat, Seattle, WA USA

[4] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[6] Ragon Inst MGH MIT & Harvard, Boston, MA USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ARYL-HYDROCARBON RECEPTOR; TRANSCRIPTION FACTOR; TH17; CELLS; TGF-BETA; IN-VIVO; ALLOGRAFT-REJECTION; HELPER TYPE-1; LINEAGE; STAT3; INTERLEUKIN-17;

D O I：

10.1038/ni.1969

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Overactive responses by interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are tightly linked to the development of autoimmunity, yet the factors that negatively regulate the differentiation of this lineage remain unknown. Here we report that the transcription factor T-bet suppressed development of the T(H)17 cell lineage by inhibiting transcription of Rorc (which encodes the transcription factor ROR gamma t). T-bet interacted with the transcription factor Runx1, and this interaction blocked Runx1-mediated transactivation of Rorc. T-bet Tyr304 was required for formation of the T-bet-Runx1 complex, for blockade of Runx1 activity and for inhibition of the T(H)17 differentiation program. Our data reinforce the idea of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell.

引用

页码：96 / U124

页数：10

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