Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation

被引：1342
作者：
Laurence, Arian
Tato, Cristina M. [1 ]
Davidson, Todd S.
Kanno, Yuka
Chen, Zhi
Yao, Zhengju
Blank, Rebecca B.
Meylan, Francoise
Siegel, Richard
Hennighausen, Lothar
Shevach, Ethan M.
O'Shea, John J.
机构：
[1] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA
[2] NIAID, Immunol Lab, Bethesda, MD 20892 USA
[3] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[4] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA
[5] NIDDKD, NIH, Bethesda, MD 20892 USA
来源：
IMMUNITY | 2007年 / 26卷 / 03期
关键词：
D O I：
10.1016/j.immuni.2007.02.009
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of ROR gamma t and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2.
引用
收藏
页码：371 / 381
页数：11
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