REV-ERBα regulates regulatory T cell function in inflammatory bowel disease [CUT&RUN]
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ABSTRACT: Colonic Rorgt+Foxp3+ Treg cells are critical to maintain intestinal homeostasis and prevent inflammatory bowel diseases by suppressing exuberant innate and adaptative immune responses. In this study, In this study, we found that REV-ERB was highly expressed in colonic RORt+Foxp3+ Treg cells and essential for their differentiation and function. Deletion of REV-ERB in Treg cells lead to diminished colonic RORt+Foxp3+ Treg cell populations even at steady state, and render mice more susceptible to TNBS and/or oxazolone-induced colitis. As a transcriptional repressor, REV-ERB can directly repress the expression of pro-inflammatory cytokines IL-17a and IL-17f, and promote RORt expression through Bhlhe40-c-maf axis in RORt+Foxp3+ Treg cells. Furthermore, REV-ERB also orchestrate RORt genome-wide distributions and co-regulate core signature genes in RORt+Foxp3+ Treg cells, including IL-10, CTLA-4, Icos, c-maf.
ORGANISM(S): Mus musculus
PROVIDER: GSE225202 | GEO | 2025/11/10
REPOSITORIES: GEO
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