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

Yann M. Kerdiles, Daniel R. Beisner, Roberto Tinoco, Anne S. Dejean, Diego H. Castrillon, Ronald A. DePinho, Stephen M. Hedrick

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329 Scopus citations

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 α-chain (IL-7Rα) 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.

Original languageEnglish (US)
Pages (from-to)176-184
Number of pages9
JournalNature Immunology
Volume10
Issue number2
DOIs
StatePublished - Jan 12 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kerdiles, Y. M., Beisner, D. R., Tinoco, R., Dejean, A. S., Castrillon, D. H., DePinho, R. A., & Hedrick, S. M. (2009). Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nature Immunology, 10(2), 176-184. https://doi.org/10.1038/ni.1689