FOXO1 regulates L-selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase

被引：144

作者：

Fabre, Stephanie ^{[1
,2
]}

Carrette, Florent ^{[1
,2
]}

Chen, Jing ^{[3
,4
]}

Lang, Valerie ^{[5
]}

Semichon, Monique ^{[1
,2
,6
]}

Denoyelle, Christine ^{[1
,2
]}

Lazar, Vladimir ^{[7
]}

Cagnard, Nicolas ^{[1
,2
]}

Dubart-Kupperschmitt, Anne ^{[1
,2
]}

Mangeney, Marianne ^{[1
,2
]}

Fruman, David A. ^{[3
,4
]}

Bismuth, Georges ^{[1
,2
]}

机构：

[1] Univ Paris 05, Inst Cochin Genet Mol, Ctr Natl Rech Sci, Unite Mixte Rech 8104,Equipe Lab Ligue Natl Contr, F-75014 Paris, France

[2] Inst Natl Sante & Rech Med, U567, Paris, France

[3] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92697 USA

[5] Ctr Invest Cooperat Assistance Publ, Prote Unit, Derio, Spain

[6] Hop Paris, Dept Rech Clin & Dev Assistance Publ, Paris, France

[7] Inst Gustave Roussy, Unite Gen Fonctionnelle, Villejuif, France

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 181卷 / 05期

关键词：

D O I：

10.4049/jimmunol.181.5.2980

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the promoter of the cell quiescence and homing regulator Kruppel-like factor 2 and regulates its expression. Together, these results reveal a new function of FOXO I in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes.

引用

页码：2980 / 2989

页数：10

共 43 条

[31] Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns [J].