Targeting pathogenic CD8⁺ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis.

ABSTRACT: Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b^-/-Il2ra^-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8⁺ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8⁺ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeri

SUBMITTER: Zhu HX 

PROVIDER: S-EPMC10997620 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature