REV-ERBa regulates regulatory T cell function in inflammatory bowel disease [RNA-seq]

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-ERBa was highly expressed in colonic RORgt+Foxp3+ Treg cells and essential for their differentiation and function. Deletion of REV-ERB in Treg cells lead to diminished colonic RORgt+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-ERBa can directly repress the expression of pro-inflammatory cytokines IL-17a and IL-17f, and promote RORgt expression through Bhlhe40-c-maf axis in RORgt+Foxp3+ Treg cells. Furthermore, REV-ERB also orchestrate RORgt genome-wide distributions and co-regulate core signature genes in RORgt+Foxp3+ Treg cells, including IL-10, CTLA-4, Icos, c-maf. Overall design: Gene expression profiling of RNA-seq data for Colon Tregs in TNBS induced colitis (REV-ERB KO and WT).