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

ABSTRACT: TH17 cells play a central role in several human autoimmune diseases. 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. Our results establish that while REV-ERBβ also acts as a negative regulator of TH17-cell function and pathogenicity, it does so in a manner that is non-redundant, independent, and unique to REV-ERBα.

ORGANISM(S): Mus musculus

PROVIDER: GSE317634 | GEO | 2026/03/27

REPOSITORIES: GEO

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Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ

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