Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor

被引：422

作者：

Kerdiles, Yann M. ^{[1
,2
]}

Beisner, Daniel R. ^{[1
,2
]}

Tinoco, Roberto ^{[1
,2
]}

Dejean, Anne S. ^{[1
,2
]}

Castrillon, Diego H. ^{[3
,4
,5
]}

DePinho, Ronald A. ^{[3
,4
,5
]}

Hedrick, Stephen M. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 02期

关键词：

TRANSCRIPTION FACTORS; PHOSPHATIDYLINOSITOL; 3-KINASE; TRANSGENIC MICE; FAMILY-MEMBER; FORKHEAD; HOMEOSTASIS; EXPRESSION; IL-7; LYMPHOCYTE; ACTIVATION;

D O I：

10.1038/ni.1689

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Foxo transcription factors have a conserved role in the adaptation of cells and organisms to nutrient and growth factor availability. Here we show that Foxo1 has a crucial, nonredundant role in T cells. In naive T cells, Foxo1 controlled the expression of the adhesion molecule L-selectin, the chemokine receptor CCR7 and the transcription factor Klf2, and its deletion was sufficient to alter lymphocyte trafficking. Furthermore, Foxo1 deficiency resulted in a severe defect in interleukin 7 receptor alpha-chain (IL-7R alpha) expression associated with its ability to bind an Il7r enhancer. Finally, growth factor withdrawal induced a Foxo1-dependent increase in Sell, Klf2 and Il7r expression. These data suggest that Foxo1 regulates the homeostasis and life span of naive T cells by sensing growth factor availability and regulating homing and survival signals.

引用

页码：176 / 184

页数：9

共 63 条

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