The Potential Role of Expression of HLA-E and HLA-G in Organ Xenotransplantation.

Xenotransplantation offers a promising solution to the shortage of human organs for transplantation but requires overcoming numerous immune responses-particularly those mediated by the innate immune system through natural killer (NK) cells and macrophages. This review examines advances demonstrating that the expression of human leukocyte antigen E (HLA-E) on porcine cells contributes to reduce cellular xenograft rejection. HLA-E expression partially inhibits both direct NK cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), while also attenuating macrophage-mediated lysis. Furthermore, perfusion of transgenic porcine organs expressing HLA-E with human blood resulted in significantly less tissue damage compared to wild-type counterparts, thereby confirming the protective effect of HLA-E against innate immunity. Inhibition of NK cell activation can be further enhanced by co-expression of HLA-G and HLA-E. These findings confirm the potential of HLA-E and HLA-G expression as a complementary strategy in the design of immune-compatible porcine organs for clinical xenotransplantation.