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

Liver tissue-resident memory T (TRM) 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 TRM cells in protective immunity and disease pathology. Comparisons between human and murine liver TRM cells reveal species-specific characteristics, suggesting the need for human-focused studies. One key finding is the involvement of liver TRM cells in viral hepatitis, where they can both control infection and contribute to liver damage. Liver TRM 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 TRM cells correlates with disease severity. In this review, we underscore the importance of liver TRM cells in vaccine development, particularly vaccines against malaria. Future research should focus on the mechanisms governing TRM-cell formation, maintenance, and function, with the aim of supporting their protective roles while mitigating detrimental effects. Advancing our understanding of liver TRM cells will enhance our knowledge of liver immunology and inform novel therapeutic strategies for liver disease management.