Progress in immunological research on innate effectors in xenotransplantation.

In xenotransplantation research, the control of innate immune cells is problematic. In this review, we focus on molecules, which are control-related findings obtained from known immune responses, and investigate whether they can be applied to control macrophages and neutrophils. The “missing-self” is a well-known recognition system for natural killer cells, but it has been shown that human leukocyte antigen (HLA)-G1, rather than HLA- E, exerts this control effect on macrophages and neutrophils. Moreover, CD47 is known as a “don’t eat me signal,” and its action can be applied to the control not only of macrophages but also of neutrophils. However, this molecule is likely influenced strongly by thrombospondin-1. In contrast, when the pulmonary surfactant protein D is converted to a membrane-type molecule, it exerts a stronger regulatory effect on macrophages and neutrophils than CD47. Regarding “contact inhibition,” the suppression of cytotoxicity by CD31 was observed in neutrophils, but not well in macrophages. In contrast, CD177, a ligand with high affinity for CD31, showed a significant regulatory effect on macrophages and neutrophils through CD31 expression. These findings are important for the future production of genetically edited pigs.