Immune cells in liver transplantation: Dual roles, mechanistic insights, and targeted therapeutic strategies.

Liver transplantation is the most effective treatment for end-stage liver disease and acute liver failure; however, organ shortage and transplant rejection remain key challenges limiting its development. In recent years, the unique role of immune cells in liver transplantation has provided new insights into the mechanisms of immune rejection and tolerance. The liver's unique immune microenvironment, dominated by innate immune cells, maintains immune tolerance through complex cell-cell interactions and cytokine networks. This article systematically reviews the dynamic roles of macrophages, neutrophils, dendritic cells (DCs), natural killer (NK) cells, and regulatory T cells (Tregs) in liver transplantation, as well as emerging therapeutic strategies derived from these findings, such as Treg infusion, machine perfusion technology, and immunometabolic regulation, all of which demonstrate immense potential. Further exploration of the heterogeneity of immune cells and their dynamic regulatory networks-particularly through the use of single-cell sequencing and spatial transcriptomics to elucidate the functional plasticity and dynamic switching mechanisms of immune cell subsets-will provide crucial guidance for achieving personalized induction of immune tolerance and optimizing liver transplant outcomes, while also laying the molecular foundation for the development of more targeted immune intervention strategies.