| First Author | Tian Y | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 481 |
| PubMed ID | 33473108 | Mgi Jnum | J:301226 |
| Mgi Id | MGI:6504771 | Doi | 10.1038/s41467-020-20786-w |
| Citation | Tian Y, et al. (2021) SOX-5 activates a novel RORgammat enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation. Nat Commun 12(1):481 |
| abstractText | T helper type 17 (Th17) cells have important functions in the pathogenesis of inflammatory and autoimmune diseases. Retinoid-related orphan receptor-gammat (RORgammat) is necessary for Th17 cell differentiation and functions. However, the transcriptional regulation of RORgammat expression, especially at the enhancer level, is still poorly understood. Here we identify a novel enhancer of RORgammat gene in Th17 cells, RORCE2. RORCE2 deficiency suppresses RORgammat expression and Th17 differentiation, leading to reduced severity of experimental autoimmune encephalomyelitis. Mechanistically, RORCE2 is looped to RORgammat promoter through SRY-box transcription factor 5 (SOX-5) in Th17 cells, and the loss of SOX-5 binding site in RORCE abolishes RORCE2 function and affects the binding of signal transducer and activator of transcription 3 (STAT3) to the RORgammat locus. Taken together, our data highlight a molecular mechanism for the regulation of Th17 differentiation and functions, which may represent a new intervening clue for Th17-related diseases. |
