The nuclear receptor REV-ERB[alpha] modulates Th17 cell-mediated autoimmune disease
In: Proceedings of the National Academy of Sciences of the United States, Jg. 116 (2019-09-10), Heft 37, S. 18528-18536
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Zugriff:
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 ROR[gamma]t. Here, we identify REV-ERB[alpha] (encoded by Nr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes ROR[gamma]t function in Th17 cells. REV-ERB[alpha] binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of ROR[gamma]t-dependent genes including Il17a and Il17f. Furthermore, elevated REV-ERB[alpha] 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-ERB[alpha] activity may be used to manipulate Th17 cells in autoimmune diseases. transcriptional repressor | autoimmunity | nuclear receptors
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The nuclear receptor REV-ERB[alpha] modulates Th17 cell-mediated autoimmune disease
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Autor/in / Beteiligte Person: | Chang, Christina ; Loo, Chin-San ; Zhao, Xuan ; Solt, Laura A. ; Liang, Yuqiong ; Bapat, Sagar P. ; Cho, Han ; Kamenecka, Theodore M. ; Leblanc, Mathias ; Atkins, Annette R. ; Yu, Ruth T. ; Downes, Michael ; Burris, Thomas P. ; Evans, Ronald M. ; Zheng, Ye |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States, Jg. 116 (2019-09-10), Heft 37, S. 18528-18536 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.1907563116 |
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