Platelet-immune cell communication in pregnancy: exploring a new frontier in maternal immunology

Pregnancy requires immune tolerance to the semiallogeneic fetus, mediated by regulatory T-cells and antiinflammatory cytokines (eg, interleukin 10 and transforming growth factor β), alongside a hypercoagulable state with elevated procoagulant factors and suppressed anticoagulants. In preeclampsia, a major cause of maternal and perinatal morbidity affecting 5% to 8% of pregnancies, excessive T-helper 1/ T-helper 17 responses, reduced Treg activity, and heightened platelet activation drive systemic inflammation, endothelial dysfunction, and microvascular thrombosis are established. Platelets, beyond hemostasis, modulate immune responses by interacting with neutrophils, monocytes, and T-cells via mediators such as P-selectin and CD40 ligand, promoting platelet-leukocyte aggregates, neutrophil extracellular traps, and proinflammatory cytokines (eg, interleukin 6 and tumor necrosis factor α). These interactions amplify coagulation via tissue factor expression, creating a pathogenic immune-hemostatic feedback loop. Deficiencies in coagulation regulators such as thrombomodulin and endothelial protein C receptor, exacerbate platelet activation and embryonic lethality, while galectins (eg, galectin 1 and 3) may mediate platelet-immune crosstalk. This article highlights the need for interdisciplinary research to elucidate these mechanisms, offering potential for novel biomarkers and therapeutic targets to improve management of vascular complications in pregnancy and maternal-fetal outcomes.