Abstract
Foxo transcription factors play an evolutionary conserved role in cellular and organismal adaptation to nutrients and growth factor availability. Here we show that, in accord with its preferential expression in lymphocytes, the transcription factor Foxo1 plays a non-redundant role in peripheral naïve T cell homeostasis. Our experiments demonstrate that in naïve T cells Foxo1 controls the expression of the homing receptors L-Selectin and Ccr7 as well as the transcription factor Klf2, and its deletion is sufficient to alter lymphocyte trafficking in vivo. In addition, Foxo1 deficiency is associated with a severe defect in IL-7Ra expression, correlated with the ability of Foxo1 to directly bind an evolutionarily conserved region upstream of the Il7ra transcriptional start site. Finally, in agreement with the regulatory mechanisms controlling Foxo activity, we show that growth factor withdrawal induces a specific Foxo1-dependent increase in L-selectin, Klf2 and IL7ra expression. Overall, these data support a model where the regulation of Foxo1 activity depending on growth factor availability regulates optimal homing and detection of survival signals.
