TGF-β Promotes Th17 Cell Development through Inhibition of SOCS3

被引：183

作者：

Qin, Hongwei ^{[2
]}

Wang, Lanfang ^{[1
]}

Feng, Ting ^{[3
]}

Elson, Charles O. ^{[1
,3
]}

Niyongere, Sandrine A. ^{[2
]}

Lee, Sun Jung ^{[2
]}

Reynolds, Stephanie L. ^{[2
]}

Weaver, Casey T. ^{[3
,4
]}

Roarty, Kevin ^{[2
]}

Serra, Rosa ^{[2
]}

Benveniste, Etty N. ^{[2
]}

Cong, Yingzi ^{[1
,3
]}

机构：

[1] Univ Alabama, Div Gastroenterol & Hepatol, Dept Med, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA

[3] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA

[4] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ROR-GAMMA-T; T(H)17 CELLS; HOST-DEFENSE; IN-VIVO; DIFFERENTIATION; GENERATION; CYTOKINE; LINEAGE; STAT3; FOXP3;

D O I：

10.4049/jimmunol.0801986

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TGF-beta, together with IL-6 and IL-21, promotes Th17 cell development. IL-6 and IL-21 induce activation of STAT3, which is crucial for Th17 cell differentiation, as well as the expression of suppressor of cytokine signaling (SOCS)3, a major negative feedback regulator of STAT3-activating cytokines that negatively regulates Th17 cells. However, it is still largely unclear how TGF-beta regulates Th17 cell development and which TGF-beta signaling pathway is involved in Th17 cell development. In this report, we demonstrate that TGF-beta inhibits IL-6- and IL-21-induced SOCS3 expression, thus enhancing as well as prolonging STAT3 activation in naive CD4(+)CD25(-) T cells. TGF-beta inhibits IL-6-induced SOCS3 promoter activity in T cells. Also, SOCS3 small interfering RNA knockdown partially compensates for the fiction of TGF-beta on Th17 cell development. In mice with a dominant-negative form of TGF-beta receptor II and impaired TGF-beta signaling, IL-6-induced CD4(+) T cell expression of SOCS3 is higher whereas STAT3 activation is lower compared with wild-type B6 CD4(+) T cells. The addition of a TGF-beta receptor I kinase inhibitor that blocks Smad-dependent TGF-beta signaling greatly, but not completely, abrogates the effect of TGF-beta on Th17 cell differentiation. Our data indicate that inhibition of SOCS3 and, thus, enhancement of STAT3 activation is at least one of the mechanisms of TGF-beta promotion of Th17 cell development. The Journal of Immunology, 2009, 183: 97-105.

引用

页码：97 / 105

页数：9

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