24-Norursodeoxycholic acid reshapes immunometabolism in CD8⁺ T cells and alleviates hepatic inflammation.

ABSTRACT:

Background & aims

24-Norursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid used to treat immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC), where dysregulated T cells including CD8⁺ T cells contribute to hepatobiliary immunopathology. We hypothesized that NorUDCA may directly modulate CD8⁺ T cell function thus contributing to its therapeutic efficacy.

Methods

NorUDCA's immunomodulatory effects were first studied in Mdr2^-/- mice, as a cholestatic model of PSC. To differentiate NorUDCA's immunomodulatory effects on CD8⁺ T cell function from its anticholestatic actions, we also used a non-cholestatic model of hepatic injury induced by an excessive CD8⁺ T cell immune respon

SUBMITTER: Zhu C 

PROVIDER: S-EPMC8522806 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature