Investigating Human Liver Tissue-Resident Memory T Cells from the Perspectives of Gastroenterologists and Hepatologists

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.