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

被引：1340

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

页码：371 / 381

页数：11

共 42 条

[41] Stat5a/b are essential for normal lymphoid development and differentiation [J].

Yao, ZJ ;

Cui, YZ ;

Watford, WT ;

Bream, JH ;

Yamaoka, K ;

Hissong, BD ;

Li, D ;

Durum, SK ;

Jiang, QO ;

Bhandoola, A ;

Hennighausen, L ;

O'Shea, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (04) :1000-1005

[42] Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense [J].

Ye, P ;

Rodriguez, FH ;

Kanaly, S ;

Stocking, KL ;

Schurr, J ;

Schwarzenberger, P ;

Oliver, P ;

Huang, WT ;

Zhang, P ;

Zhang, J ;

Shellito, JE ;

Bagby, GJ ;

Nelson, S ;

Charrier, K ;

Peschon, JJ ;

Kolls, JK .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (04) :519-527

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