期刊
IMMUNITY
卷 45, 期 4, 页码 774-787出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.09.010
关键词
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类别
资金
- Inserm Dotation (Nouveau-recrute)
- ANR [ANR-09-RPDOC-015-01]
- ARSEP Foundation [R112195BB]
- Midi-Pyrenees Region
- ARSEP Fondation [R14067BB]
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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