The role of natural killer cells in the immune response after liver transplantation

Abstract

Natural killer (NK) cells are crucial components of the innate immune system and are abundantly present in the liver, a unique immune organ frequently subjected to clinical transplantation. NK cells regulate their functional state through a finely tuned balance between activating and inhibitory receptors, allowing them to eliminate target cells independently of major histocompatibility complex class I (MHC-I) restriction. In the context of liver transplantation, NK cells respond dynamically to ischemia-reperfusion injury, donor-recipient immune mismatch and immunosuppressive treatments, thereby influencing graft acceptance, rejection and infection control. Activated NK cells release a broad range of cytokines and chemokines, shaping both innate and adaptive immune responses. This review highlights the multifaceted roles of NK cells in transplant immunity, emphasizes their clinical and translational significance, and summarizes emerging therapeutic strategies that target NK cells. Collectively, it provides insights into NK cell biology and underscores their potential in improving long-term outcomes after liver transplantation.