| First Author | Zhang J | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 10 | Pages | 3397-3406 |
| PubMed ID | 29632143 | Mgi Jnum | J:261497 |
| Mgi Id | MGI:6155434 | Doi | 10.4049/jimmunol.1800193 |
| Citation | Zhang J, et al. (2018) TCF-1 Inhibits IL-17 Gene Expression To Restrain Th17 Immunity in a Stage-Specific Manner. J Immunol 200(10):3397-3406 |
| abstractText | T cell factor 1 (TCF-1) is expressed in both developing and mature T cells and has been shown to restrain mature T cell-mediated Th17 responses by inhibiting IL-17 expression. However, it is not clear when TCF-1 is required in vivo to restrain the magnitude of peripheral Th17 responses and what the molecular mechanisms responsible for TCF-1-regulated IL-17 gene expression are. In this study, we showed that conditional deletion of TCF-1 at the early but not later CD4(+)CD8(+) double-positive stage in mice enhanced Th17 differentiation and aggravated experimental autoimmune encephalomyelitis, which correlates with abnormally high IL-17 expression. Expression of TCF-1 in TCF-1-deficient thymocytes but not TCF-1-deficient Th17 cells inhibited IL-17 expression. TCF-1 binds to IL-17 promoter regions, and deletion of two TCF-1 binding sites relieves TCF-1-mediated inhibition of IL-17 promoter activity. Lastly, wild-type TCF-1, but not a TCF-1 mutant that has no intrinsic histone deacetylase activity, was able to inhibit IL-17 expression in TCF-1 deficient mouse thymocytes. Thus, our study demonstrates the requirement of TCF-1 in vivo at stages earlier than double-positive cells to restrain peripheral Th17 immunity by directly binding and inhibiting IL-17 promoter in its intrinsic histone deacetylase-dependent manner. |
