iNKT cell development is orchestrated by different branches of TGF-β signaling

被引：71

作者：

Doisne, Jean-Marc ^{[1
]}

Bartholin, Laurent ^{[2
,6
,7
,9
]}

Yan, Kai-Ping ^{[4
]}

Garcia, Celine N. ^{[3
,6
,8
]}

Duarte, Nadia ^{[1
]}

Le Luduec, Jean-Benoit ^{[5
,6
]}

Vincent, David ^{[2
,6
,7
,9
]}

Cyprian, Farhan ^{[3
,6
,8
]}

Horvat, Branka ^{[3
,6
,8
]}

Martel, Sylvie ^{[2
,6
,7
,9
]}

Rimokh, Ruth ^{[2
,6
,7
]}

Losson, Regine ^{[4
]}

Benlagha, Kamel ^{[1
]}

Marie, Julien C. ^{[3
,6
,8
]}

机构：

[1] Univ Descartes, Hop Cochin St Vincent de Paul, INSERM, U561,Grp AVENIR, F-75014 Paris, France

[2] INSERM, U590, IFR62, F-69008 Lyon, France

[3] INSERM, U758, IFR128, F-69007 Lyon, France

[4] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[5] INSERM, U851, IFR128, F-69007 Lyon, France

[6] Univ Lyon, F-69003 Lyon, France

[7] Ctr Leon Berard, F-69008 Lyon, France

[8] Ecole Normale Super Lyon, F-69007 Lyon, France

[9] INSERM, U590, Grp AVENIR, F-69008 Lyon, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2009年 / 206卷 / 06期

关键词：

NKT CELLS; T-CELLS; HOMEOSTASIS; GROWTH; LYMPHOTOXIN; MECHANISMS; EXPRESSION; MATURATION; PRECURSOR; PATHWAYS;

D O I：

10.1084/jem.20090127

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1 gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1 gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.

引用

页码：1365 / 1378

页数：14

共 35 条

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