Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells

Anne S. Dejean, Daniel R. Beisner, Irene L. Ch'en, Yann M. Kerdiles, Anna Babour, Karen C. Arden, Diego H. Castrillon, Ronald A. DePinho, Stephen M. Hedrick

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153 Scopus citations

Abstract

Foxo transcription factors regulate cell cycle progression, cell survival and DNA-repair pathways. Here we demonstrate that deficiency in Foxo3 resulted in greater expansion of T cell populations after viral infection. This exaggerated expansion was not T cell intrinsic. Instead, it was caused by the enhanced capacity of Foxo3-deficient dendritic cells to sustain T cell viability by producing more interleukin 6. Stimulation of dendritic cells mediated by the coinhibitory molecule CTLA-4 induced nuclear localization of Foxo3, which in turn inhibited the production of interleukin 6 and tumor necrosis factor. Thus, Foxo3 acts to constrain the production of key inflammatory cytokines by dendritic cells and to control T cell survival.

Original languageEnglish (US)
Pages (from-to)504-513
Number of pages10
JournalNature Immunology
Volume10
Issue number5
DOIs
StatePublished - 2009

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ASJC Scopus subject areas

  • Immunology

Cite this

Dejean, A. S., Beisner, D. R., Ch'en, I. L., Kerdiles, Y. M., Babour, A., Arden, K. C., Castrillon, D. H., DePinho, R. A., & Hedrick, S. M. (2009). Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nature Immunology, 10(5), 504-513. https://doi.org/10.1038/ni.1729