| Title | Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Ouyang X, Zhang R, Yang J, Li Q, Qin L, Zhu C, Liu J, Ning H, Shin MSun, Gupta M, Qi C-F, He JCijiang, Lira SA, Morse HC, Ozato K, Mayer L, Xiong H |
| Journal | Nat Commun |
| Volume | 2 |
| Pagination | 314 |
| Date Published | 2011 |
| ISSN | 2041-1723 |
| Keywords | Animals, Cell Differentiation, Cell Lineage, Female, Gene Silencing, Interferon Regulatory Factors, Interleukin-17, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Sequence Deletion, Th17 Cells |
| Abstract | T(H)17 cells are recognized as a unique subset of T helper cells that have critical roles in the pathogenesis of autoimmunity and tissue inflammation. Although RORγt is necessary for the generation of T(H)17 cells, the molecular mechanisms underlying the functional diversity of T(H)17 cells are not fully understood. Here we show that a member of interferon regulatory factor (IRF) family of transcription factors, IRF8, has a critical role in silencing T(H)17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient T(H)17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced T(H)17 phenotype. IRF8 was induced steadily and inhibited T(H)17-cell differentiation during T(H)17 lineage commitment at least in part through its physical interaction with RORγt. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of T(H)17-cell differentiation. |
| DOI | 10.1038/ncomms1311 |
| Alternate Journal | Nat Commun |
| PubMed ID | 21587231 |
| Grant List | / ImNIH / Intramural NIH HHS / United States |
Related Faculty:
Lihui Qin, M.D., Ph.D.