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 enhances 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 in TH17 cells. REV-ERBβ does not appear to strongly rely on interaction with the classic co-repressor NCoR1 to regulate gene expression, 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.
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BibTeX
@article{campbell2026negative,
title = {{Negative regulation of TH17-mediated inflammation by the nuclear receptor REV-ERBβ}},
author = {Sean Campbell and Sarah A. Mosure and Mohammed Amir and Jonathan Chuck and Qun Lu and Laura A. Solt},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117577},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)02956-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Negative regulation of TH17-mediated inflammation by the nuclear receptor REV-ERBβ
AU - Sean Campbell
AU - Sarah A. Mosure
AU - Mohammed Amir
AU - Jonathan Chuck
AU - Qun Lu
AU - Laura A. Solt
PY - 2026
DA - 2026/10/15
JO - iScience
DO - 10.1016/j.isci.2026.117577
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)02956-1
AB - 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 enhances 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 in TH17 cells. REV-ERBβ does not appear to strongly rely on interaction with the classic co-repressor NCoR1 to regulate gene expression, 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.
SN - 2589-0042
ER -