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Nat Immunol. 2009 Feb;10(2):176-84. doi: 10.1038/ni.1689. Epub 2009 Jan 11.

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

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  • 1Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, California 92093-0377, USA.

Abstract

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-7Ralpha) 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.

PMID:
19136962
[PubMed - indexed for MEDLINE]
PMCID:
PMC2856471
Free PMC Article
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