Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3+ regulatory T cells

被引：373

作者：

Gandhi, Roopali ^{[1
]}

Kumar, Deepak

Burns, Evan J. ^{[1
]}

Nadeau, Meghan ^{[1
]}

Dake, Ben ^{[1
]}

Laroni, Alice ^{[1
]}

Kozoriz, Deneen ^{[1
]}

Weiner, Howard L. ^{[1
]}

Quintana, Francisco J. ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med, Boston, MA 02115 USA

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 09期

基金：

美国国家卫生研究院;

关键词：

TRANSCRIPTION FACTOR FOXP3; DNA-BINDING PROTEINS; FACTOR C-MAF; TGF-BETA; GENE-EXPRESSION; DIFFERENTIATION; IKAROS; INDUCTION; TOLERANCE; RESPONSES;

D O I：

10.1038/ni.1915

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T cells (T-reg cells) and interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells), but its role in human T cell differentiation is unknown. We investigated the role of AhR in the differentiation of human induced T-reg cells (iT(reg) cells). We found that AhR activation promoted the differentiation of CD4(+) Foxp3(-) T cells, which produce IL-10 and control responder T cells through granzyme B. However, activation of AhR in the presence of transforming growth factor-beta 1 induced Foxp3(+) iT(reg) cells, which suppress responder T cells through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of functional Foxp3(+) iT(reg) cells required coordinated action of the transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target through which functional iT(reg) cells could be induced in human autoimmune disorders.

引用

页码：846 / U103

页数：9

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