| First Author | Wang Y | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 3 | Pages | 355-66 |
| PubMed ID | 24530058 | Mgi Jnum | J:209915 |
| Mgi Id | MGI:5568903 | Doi | 10.1016/j.immuni.2014.01.002 |
| Citation | Wang Y, et al. (2014) The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-gamma-producing T helper 17 cells. Immunity 40(3):355-66 |
| abstractText | T helper 17 (Th17) cells can give rise to interleukin-17A (IL-17A)- and interferon (IFN)-gamma-double-producing cells that are implicated in development of autoimmune diseases. However, the molecular mechanisms that govern generation of IFN-gamma-producing Th17 cells are unclear. We found that coexpression of the Th1 and Th17 cell master transcription factors, T-bet and retinoid-related orphan receptor gamma-t (RORgammat), respectively, did not generate Th cells with robust IL-17 and IFN-gamma expression. Instead, development of IFN-gamma-producing Th17 cells required T-bet and Runx1 or Runx3. IL-12-stimulated Th17 cells upregulated Runx1, which bound to the Ifng locus in a T-bet-dependent manner. Reciprocally, T-bet or Runx1 deficiency or inhibition of Runx transcriptional activity impaired the development of IFN-gamma-producing Th17 cells during experimental autoimmune encephalomyelitis, which correlated with substantially ameliorated disease course. Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-gamma-producing Th17 cells. |
