Hepatic immune environment differences among common mouse strains in models of MASH and liver cancer.

Background & Aims: Inbred mouse strains are critical tools for studying immune regulation of metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Here, we profiled mouse strain-associated hepatic immune differences, and performed mice-human cross-species immune comparisons. Methods: Immune landscapes of C57BL/6, BALB/c, and FVB/N mice were compared under healthy, MASH, or HCC state using high-dimensional spectral flow cytometry (n = 4 per condition). MASH was induced by feeding methionine- and choline-deficient or Western diet + carbon tetrachloride. HCC was caused by hydrodynamic plasmid injection of MYC/sg-p53. Public mouse and human scRNA-seq datasets were used for validation and cross-species comparisons. Results: In healthy mice, liver CD4 Conclusions: Substantial liver immune differences exist among common mouse strains. Mice can recapitulate certain human liver immune changes with strain variations. Impact and implications: Our immune cell profiling study revealed that the liver immune environment can be quite different among common mouse strains both under healthy and pathologic states, such as steatohepatitis or neoplastic processes. Our results serve as a data resource for studies investigating liver immunology and provide valuable insights for the design of studies on various immune cells in the livers of mice.