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

Nat Immunol. 2009 May;10(5):504-13. doi: 10.1038/ni.1729. Epub 2009 Apr 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Arenaviridae Infections / immunology
  • Blotting, Western
  • CTLA-4 Antigen
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Congenic
  • Mice, Transgenic
  • Protein Transport / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, CD
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • FoxO3 protein, mouse
  • Interleukin-6
  • Tumor Necrosis Factor-alpha