| First Author | Chang C | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 37 | Pages | 18528-18536 |
| PubMed ID | 31455731 | Mgi Jnum | J:279306 |
| Mgi Id | MGI:6360505 | Doi | 10.1073/pnas.1907563116 |
| Citation | Chang C, et al. (2019) The nuclear receptor REV-ERBalpha modulates Th17 cell-mediated autoimmune disease. Proc Natl Acad Sci U S A 116(37):18528-18536 |
| abstractText | T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor RORgammat. Here, we identify REV-ERBalpha (encoded by Nr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes RORgammat function in Th17 cells. REV-ERBalpha binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORgammat-dependent genes including Il17a and Il17f Furthermore, elevated REV-ERBalpha expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE). These results suggest that modulating REV-ERBalpha activity may be used to manipulate Th17 cells in autoimmune diseases. |
