Effects of NorUDCA on the Transcriptomic Landscape of Differentiating Murine Pathogenic Th17 Cells In Vitro

24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver disease, such as primary sclerosing cholangitis (PSC). Since PSC strongly associates with TH17-mediated tissue inflammation, we explored NorUDCA’s immunomodulatory potential on TH17 cells. Using an unbiased bulk RNA sequencing approach, we discovered that brief exposure (4 hour) to NorUDCA reshapes transcriptomic landscape of murine pathogenic (p)TH17 cells with top enriched pathways of mTORC1 signaling, hypoxia, Myc and associated metabolic processes, such as glycolysis and OXPHOS. NorUDCA treatment also modulates expression of several genes involved in KEGG glutamine pathway, indicating NorUDCA might affect pTH17 cell glutamine metabolism. Taken together, our bulk RNA sequencing data demonstrate NorUDCA’s therapeutic efficacy in modulating pTH17 immunometabolism, potentiating future clinical applications for treating TH17-mediated disease and beyond. Transcriptomic profiling of murine pathogenic TH17 cells in the presence with or without 4-hour NorUDCA treatment