Platelet-Immune Cell Communication in Pregnancy: Exploring a New Frontier in Maternal Immunology.

Abstract

Pregnancy requires immune tolerance to the semi-allogeneic fetus, mediated by regulatory T-cells and anti-inflammatory cytokines (e.g., IL-10, TGF-β), alongside a hypercoagulable state with elevated procoagulant factors and suppressed anticoagulants. In preeclampsia (PE), a major cause of maternal and perinatal morbidity affecting 5-8% of pregnancies, excessive Th1/Th17 responses, reduced Treg activity, and heightened platelet activation drive systemic inflammation, endothelial dysfunction, and microvascular thrombosis is established. Platelets, beyond hemostasis, modulate immune responses by interacting with neutrophils, monocytes, and T-cells via mediators like P-selectin and CD40 ligand, promoting platelet-leukocyte aggregates, neutrophil extracellular traps (NETs), and pro-inflammatory cytokines (e.g., IL-6, TNF-α). These interactions amplify coagulation via tissue factor expression, creating a pathogenic immune-hemostatic feedback loop. Deficiencies in coagulation regulators like thrombomodulin and endothelial protein C receptor exacerbate platelet activation and embryonic lethality, while galectins (e.g., galectin-1, -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.