Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives

Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and supporting maternal-fetal homeostasis throughout human pregnancy. Clinical and experimental evidence demonstrates that dysregulation of peripheral and decidual Tregs manifested as quantitative deficits, impaired suppressive function or lineage instability increased the risk of various pathological pregnancies, such as recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA), pre-eclampsia (PE) and preterm birth (PTB). Recently, novel therapeutic strategies targeting Tregs have emerged in oncology, transplantation, and autoimmune diseases. However, their application in pathological pregnancy remains in its infancy. This review outlines the spatiotemporal dynamics of peripheral and decidual Tregs throughout gestation, elucidating their roles in maintaining maternal-fetal homeostasis and their dysregulation in pathological pregnancies. We also critically evaluated the therapeutic strategies targeting Tregs and Tregs-associated signaling pathways, including hormonal support, traditional intravenous immunoglobulin, as well as emerging interventions such as immunometabolic reprogramming and engineered cellular therapies like chimeric antigen receptor Tregs. This review may provide insights for understanding the roles of Tregs in physiological and pathological pregnancy, as well as provide new idea in the immunotherapy of pathological pregnancy.