Maternal-fetal interface immune regulation and placental development: From physiological remodeling to pathological mechanisms underlying adverse pregnancy outcomes.

The maternal-fetal interface (MFI) serves as a crucial bidirectional crosstalk site between the mother and the developing fetus, wherein precisely orchestrated immune regulatory networks are indispensable for sustaining tolerance toward the semi-allogeneic fetus while concurrently defending effectively against pathogenic challenges. Excessive inflammatory activation can perturb immune homeostasis at the MFI, particularly during the first trimester, and can compromise placental development and function, thereby contributing to adverse pregnancy outcomes, including recurrent spontaneous abortion, preeclampsia of placental origin, and even aberrant embryonic development. Therefore, a detailed understanding of the cellular composition of the MFI and its dynamic relationship with placental development is fundamental to elucidating disease etiology and informing interventional research on placenta-related pregnancy complications. This review summarizes the major immune cell populations present at the MFI (namely T cells, decidual Natural Killer cells and decidual macrophages) and their functional characteristics, examines their roles in physiological placental formation and remodeling, and evaluates their associations with several common adverse pregnancy outcomes. Collectively, the findings highlight the central role of major maternal immune cells in establishing immune tolerance during early gestation and underscore the potential clinical value of immune profiling in predicting and managing adverse pregnancy outcomes.