MiR-519d-3p from Placenta-Derived Exosomes Induce Immune Intolerance Regulating Immune Cells, Contributing to the Pathogenesis of Preeclampsia

Abstract

Background: MiR-519d-3p, also called specific placenta biomarkers, is a member of the Chromosome 19 miRNA Cluster (C19MC) with the highest concentrations of miRNAs in human placenta and maternal serum. These miRNAs are secreted by fetal trophoblast cells within extracellular vesicles (EVs) and interact with the mother's immune cells, which has been proposed to be crucial for immunological tolerance at the placental-maternal interface. A key mechanism in preeclampsia, a multifactorial, multipath hypertensive pregnancy illness, is an immunological imbalance between the mother and the fetus.

Methods: Using Next Generation Sequencing, we determined that the placenta-derived Exosomes (pEXOs) of preeclamptic patients had elevated expression of miR-519. To further develop an in vitro model of trophoblast-immune cell communication, HTR-8/Svneo cells and Jurkat T cells were employed and we utilized experiments such as Western blot (WB), Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), Cell-Counting-Kit-8 (CCK-8) cell proliferation analysis, cell apoptosis analysis, and other techniques to accomplish research.

Results: It was discovered that miR-519d-3p in pEXOs promoted Jurkat T cell proliferation, inhibited apoptosis, and induced Jurkat T cell differentiation toward Th17.

Conclusion: MiR-519d-3p in pEXOs disrupts immune tolerance at the maternal-placental interface by encouraging Jurkat T cell proliferation, preventing Jurkat T cell apoptosis, and creating an imbalance in Th17/Treg differentiation. This likely leads to SIRS and unfavorable pregnancy complications like preeclampsia.

Keywords: Immune imbalance; Jurkat T cells; miR-519d-3p; placenta-derived exosome.