Foxo3 transcription factor drives pathogenic T helper 1 differentiation by inducing the expression of eomes - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Immunity Year : 2016

Foxo3 transcription factor drives pathogenic T helper 1 differentiation by inducing the expression of eomes

Abstract

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-gamma (IFN-gamma) and granulocyte monocyte colony stimulating factor (GMCSF). 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-gamma 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.
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Dates and versions

hal-02631699 , version 1 (28-10-2024)

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Caroline Stienne, Michael Michieletto, Mehdi Benamar, Nadège Carrié, Isabelle Bernard-Cadenat, et al.. Foxo3 transcription factor drives pathogenic T helper 1 differentiation by inducing the expression of eomes. Immunity, 2016, 45 (4), pp.774-787. ⟨10.1016/j.immuni.2016.09.010⟩. ⟨hal-02631699⟩
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