Negative regulation of TH17-mediated inflammation by the nuclear receptor REV-ERBβ

We and others reported the nuclear receptor REV-ERBα as a cell-intrinsic repressor of TH17-mediated pathogenicity. REV-ERBβ, REV-ERBα’s closely related family member, is thought to be functionally redundant to REV-ERBα, which we sought to explore in TH17-mediated immunity.

Our data indicate that deletion of REV-ERBβ enhanced TH17-mediated pro-inflammatory cytokine expression and exacerbated disease in mouse models of multiple sclerosis and colitis. RNA-sequencing indicates REV-ERBβ and REV-ERBα do not have similar transcriptional profiles. REV-ERBβ does not appear to regulate gene expression through interaction with the classic co-repressor NCoR1, which is in contrast to REV-ERBα in TH17 cells, nor does it utilize heme, its known endogenous ligand for its repressive functions.