Foxo3 drives pathogenic Th1 differentiation

We showed that the transcription factor Foxo3 played a specific role in the polarization of CD4+ T cells towards pathogenic Th1 cells producing both interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). To understand the molecular mechanisms whereby Foxo3 controls CD4+ T cell differentiation, unbiased analysis of genes differentially expressed in Foxo3-deficient vs. Foxo3-sufficient CD4+ T cells was achieved using both resting and activated CD4+ T cells obtained following 12 or 24 hours of stimulation with anti-CD3 mAbs. Gene expression analysis were performed on purified naive CD4+ T cells from Foxo3-/- (n=4) or WT (n=4) littremate controls either unstimulated (T0) or stimulated with 2 μg/ml of anti-CD3 mAbs for 12 (T12) or 24 (T24) hours