The unique expression pattern of human leukocyte antigen in trophoblasts potentially explains the key mechanism of maternal-fetal tolerance and successful pregnancy

Abstract

The success of pregnancy mainly depends on immune tolerance of the mother for the semi-allogeneic fetus. The placenta carrying paternal antigens develops in the maternal uterus without suffering immune attack, making the underlying mechanism of maternal tolerance an enduring mystery. As we all know, human leukocyte antigen (HLA) plays an important role in antigen processing and presentation, thus inducing specific immune responses. Therefore, it is reasonable to speculate that the absence of classical HLA class-I（HLA-I) and HLA class-II (HLA-II) molecules in trophoblasts may account for the maternal-fetal tolerance. Here, we review the HLA-involved interactions between trophoblast cells and decidual immune cells, which contribute to the immunotolerance in the development of normal pregnancy. We also compare the similarity between the maternal-fetal interface and tumor-immune microenvironment because the important role of HLA molecules in tumor immune invasion can provide some references to studies of maternal-fetal immune tolerance. Besides, the abnormal HLA expression is likely to be associated with unexplained miscarriage, making HLA molecules potential therapeutic targets. The advances reported by these studies may exert profound influences on other research areas, including tumor immunity, organ transplantation and autoimmune disease in the future.

Keywords: Decidual immune cells; Human leukocyte antigen; Mater-fetal tolerance; Maternal-fetal interface; Miscarriage; Trophoblast.