Foxp3+ Regulatory T Cells Promote T Helper 17 Cell Development In Vivo through Regulation of Interleukin-2

被引：132

作者：

Chen, Yi ^{[1
]}

Haines, Christopher J. ^{[1
]}

Gutcher, Ilona ^{[2
]}

Hochweller, Kristin ^{[3
]}

Blumenschein, Wendy M. ^{[1
]}

McClanahan, Terrill ^{[1
]}

Haemmerling, Guenter ^{[3
]}

Li, Ming O. ^{[2
]}

Cua, Daniel J. ^{[1
]}

McGeachy, Mandy J. ^{[1
]}

机构：

[1] Merck Res Labs, Palo Alto, CA 94304 USA

[2] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[3] German Canc Res Ctr, Div Mol Immunol, D-69120 Heidelberg, Germany

来源：

IMMUNITY | 2011年 / 34卷 / 03期

关键词：

TGF-BETA; TH17; CELLS; IFN-GAMMA; DIFFERENTIATION; INDUCTION; T(H)17; IL-2; INFLAMMATION; HOMEOSTASIS; EXPRESSION;

D O I：

10.1016/j.immuni.2011.02.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T helper 17 (Th17) cell development is driven by cytokines including transforming growth factor-beta (TGF-beta), interleukin-6 (IL-6), IL-1, and IL-23. Regulatory T (Treg) cells can provide the TGF-beta in vitro, but their role in vivo remains unclear, particularly because Treg Th17 cell-associated autoimmunity. We used mice expressing Diphtheria toxin receptor under control of the Foxp3 promoter to deplete Foxp3(+) Treg cells in adult mice during in vivo Th17 cell priming. Treg cell depletion resulted in a reduced frequency of antigen-specific IL-17 producers in draining lymph nodes and blood, correlating with reduced inflammatory skin responses. In contrast, Treg cells did not promote IL-17 secretion after initial activation stages. Treg cell production of TGF-beta was not required for Th17 cell promotion, and neither was suppression of Th1 cell-associated cytokines. Rather, regulation of IL-2 availability and resultant signaling through CD25 by Treg cells was found to play an important role.

引用

页码：409 / 421

页数：13

共 41 条

[1] CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production [J].