| First Author | Lainé A | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 4 | Pages | 1791-803 |
| PubMed ID | 26170390 | Mgi Jnum | J:323791 |
| Mgi Id | MGI:6838897 | Doi | 10.4049/jimmunol.1500849 |
| Citation | Laine A, et al. (2015) Foxo1 Is a T Cell-Intrinsic Inhibitor of the RORgammat-Th17 Program. J Immunol 195(4):1791-803 |
| abstractText | An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator of the Th17 program. Using mixed bone marrow chimeras and Foxo1-deficient mice, we demonstrate that this control is effective in vivo, as well as in vitro during differentiation assays of naive T cells with specific inhibitor of Foxo1 or inhibitors of the PI3K/Akt pathway acting upstream of Foxo1. Consistently, expressing this transcription factor in T cells strongly decreases Th17 generation in vitro as well as transcription of both IL-17A and IL-23R RORgammat-target genes. Finally, at the molecular level, we demonstrate that Foxo1 forms a complex with RORgammat via its DNA binding domain to inhibit RORgammat activity. We conclude that Foxo1 is a direct antagonist of the RORgammat-Th17 program acting in a T cell-intrinsic manner. |
