Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells

被引：665

作者：

Sefik, Esen ^{[1
]}

Geva-Zatorsky, Naama ^{[1
]}

Oh, Sungwhan ^{[1
]}

Konnikova, Liza ^{[4
,5
]}

Zemmour, David ^{[1
]}

McGuire, Abigail Manson ^{[6
]}

Burzyn, Dalia ^{[1
]}

Ortiz-Lopez, Adriana ^{[1
]}

Lobera, Mercedes ^{[7
]}

Yang, Jianfei ^{[7
]}

Ghosh, Shomir ^{[7
]}

Earl, Ashlee ^{[6
]}

Snapper, Scott B. ^{[4
,5
]}

Jupp, Ray ^{[8
]}

Kasper, Dennis ^{[1
]}

Mathis, Diane ^{[1
,2
,3
]}

Benoist, Christophe ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[7] Tempero Pharmaceut, Cambridge, MA 02139 USA

[8] UCB Pharma, Slough, Berks, England

来源：

SCIENCE | 2015年 / 349卷 / 6251期

关键词：

TH17; CELLS; DIFFERENTIATION; GAMMA; T(H)17; INFLAMMATION; HOMEOSTASIS; METABOLITES; MECHANISMS; GENERATION; MICROBIOTA;

D O I：

10.1126/science.aaa9420

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：

T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T-regs) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T-reg population in the mouse colon, which constrains immunoinflammatory responses. This induction-which we find to map to a broad, but specific, array of individual bacterial species-requires the transcription factor Ror gamma, paradoxically, in that Ror gamma is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Ror gamma's transcriptional footprint differs in colonic T-regs and T(H)17 cells and controls important effector molecules. Ror gamma, and the T-regs that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Ror gamma results in very different outcomes even in closely related cell types.

引用

页码：993 / 997

页数：5

共 31 条

[31] TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function [J].

Zhou, Liang ;

Lopes, Jared E. ;

Chong, Mark M. W. ;

Ivanov, Ivaylo I. ;

Min, Roy ;

Victora, Gabriel D. ;

Shen, Yuelei ;

Du, Jianguang ;

Rubtsov, Yuri P. ;

Rudensky, Alexander Y. ;

Ziegler, Steven F. ;

Littman, Dan R. .

NATURE, 2008, 453 (7192) :236-U14

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