| First Author | Stienne C | Year | 2016 |
| Journal | Immunity | Volume | 45 |
| Issue | 4 | Pages | 774-787 |
| PubMed ID | 27742544 | Mgi Jnum | J:258956 |
| Mgi Id | MGI:6140975 | Doi | 10.1016/j.immuni.2016.09.010 |
| Citation | Stienne C, et al. (2016) Foxo3 Transcription Factor Drives Pathogenic T Helper 1 Differentiation by Inducing the Expression of Eomes. Immunity 45(4):774-787 |
| abstractText | 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 (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-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. |
