Abstract
Liver tissue-resident memory T (T(RM)) cells play a pivotal role in hepatic immune responses. Their unique residence within liver sinusoids allow continuous antigen surveillance. In this review, we highlight the role of liver T(RM) cells in protective immunity and disease pathology. Comparisons between human and murine liver T(RM) cells reveal species-specific characteristics, suggesting the need for human-focused studies. One key finding is the involvement of liver T(RM) cells in viral hepatitis, where they can both control infection and contribute to liver damage. Liver T(RM) cells also exhibit dual roles in metabolic-associated steatotic liver disease, promoting inflammation and fibrosis while also contributing to fibrosis resolution. In autoimmune liver diseases, such as autoimmune hepatitis and primary sclerosing cholangitis, the presence of liver T(RM) cells correlates with disease severity. In this review, we underscore the importance of liver T(RM) cells in vaccine development, particularly vaccines against malaria. Future research should focus on the mechanisms governing T(RM)-cell formation, maintenance, and function, with the aim of supporting their protective roles while mitigating detrimental effects. Advancing our understanding of liver T(RM) cells will enhance our knowledge of liver immunology and inform novel therapeutic strategies for liver disease management.