The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease.

Published

Journal Article

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 RORγt. Here, we identify REV-ERBα (encoded by Nr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes RORγt function in Th17 cells. REV-ERBα binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORγt-dependent genes including Il17a and Il17f Furthermore, elevated REV-ERBα 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-ERBα activity may be used to manipulate Th17 cells in autoimmune diseases.

Full Text

Duke Authors

Cited Authors

  • Chang, C; Loo, C-S; Zhao, X; Solt, LA; Liang, Y; Bapat, SP; Cho, H; Kamenecka, TM; Leblanc, M; Atkins, AR; Yu, RT; Downes, M; Burris, TP; Evans, RM; Zheng, Y

Published Date

  • September 2019

Published In

Volume / Issue

  • 116 / 37

Start / End Page

  • 18528 - 18536

PubMed ID

  • 31455731

Pubmed Central ID

  • 31455731

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1907563116

Language

  • eng