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

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