Decreased PD-L1 contributes to preeclampsia by suppressing GM-CSF via the JAK2/STAT5 signal pathway.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 have been detected at the materno-embryonic interface in both human and murine pregnancy models. However, research regarding the PD-1/PD-L1 signal in preeclampsia (PE) is limited. In the present investigation, 30 normal pregnant females and 30 PE patients were enrolled. Cellular functional experiments were performed in two trophoblast cell lines by transfection with lentiviral vectors for overexpression and down-regulation of PD-L1. The placental expressions of PD-1, PD-L1, and granulocyte macrophage colony-stimulating factor (GM-CSF) exhibited a notable reduction in PE cases compared with healthy pregnancies. Cellular functional experiments indicated that excessive PD-L1 expression significantly enhanced trophoblast migratory, invasive, and proliferative capabilities while inhibiting cell apoptosis. Additionally, the administration of lentivirus-mediated PD-L1 overexpression could alleviate clinical symptoms (hypertension, proteinuria) of PE-like rats. Therefore, decreased PD-L1 may contribute to PE by inhibiting GM-CSF via activating the JAK2/STAT5 pathway. Our study provides a novel pathway that can be targeted for the therapy of this disease.