REV-ERBa regulates regulatory T cell function in inflammatory bowel disease [CUT&RUN]

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 ROR?t+Foxp3+ Treg cells and essential for their differentiation and function. Deletion of REV-ERB in Treg cells lead to diminished colonic ROR?t+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 ROR?t expression through Bhlhe40-c-maf axis in ROR?t+Foxp3+ Treg cells. Furthermore, REV-ERB also orchestrate ROR?t genome-wide distributions and co-regulate core signature genes in ROR?t+Foxp3+ Treg cells, including IL-10, CTLA-4, Icos, c-maf. Overall design: Cleavage Under Targets and Release Using Nuclease (cut&run) for transcription factors RVBa, Foxp3, RORgt, c-maf and BHLHE40 in induced RORgt+iTreg cells.