- Stienne, Caroline;
- Michieletto, Michaël F;
- Benamar, Mehdi;
- Carrié, Nadège;
- Bernard, Isabelle;
- Nguyen, Xuan-Hung;
- Lippi, Yannick;
- Duguet, Fanny;
- Liblau, Roland S;
- Hedrick, Stephen M;
- Saoudi, Abdelhadi;
- Dejean, Anne S
The transcription factor Foxo3 plays a crucial role in myeloid cell function but its role in lymphoid cells remains poorly defined. Here, we have shown that Foxo3 expression was increased after T cell receptor engagement and played a specific role in the polarization of CD4+ T cells toward pathogenic T helper 1 (Th1) cells producing interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). Consequently, Foxo3-deficient mice exhibited reduced susceptibility to experimental autoimmune encephalomyelitis. At the molecular level, we identified Eomes as a direct target gene for Foxo3 in CD4+ T cells and we have shown that lentiviral-based overexpression of Eomes in Foxo3-deficient CD4+ T cells restored both IFN-γ and GM-CSF production. Thus, the Foxo3-Eomes pathway is central to achieve the complete specialized gene program required for pathogenic Th1 cell differentiation and development of neuroinflammation.