Placenta exosomal miRNA-30d-5p facilitates decidual macrophage polarization by targeting HDAC9

Abstract Pregnancy involves a wide range of adaptations in the maternal body. Maternal immune tolerance toward the foreign fetus is critical for a successful pregnancy. Decidual macrophages are the primary antigen-presenting and phagocytic cells responsible for antigen presentation and apoptotic cell removal. Their phenotype changes dynamically during pregnancy. Placenta-derived exosomes are small vesicles carrying active biological molecules such as microRNAs, proteins, and lipids. The placenta-derived exosomes have been implicated in endothelial cell activation, smooth muscle cell migration, and T-cell apoptosis, but it is unknown whether placenta-derived exosomes would affect the development and functions of decidual macrophages. In this study, we reported that placenta-derived exosomes stimulated macrophage polarization into alternatively activated (M2) macrophages. Mechanistically, miRNA-30d-5p from the placenta-derived exosomes induced macrophage polarization to the M2 phenotype by targeting histone deacetylase 9. Furthermore, the conditioned medium of placenta-derived exosome–treated macrophages promoted trophoblast migration and invasion. By contrast, the conditioned medium impaired the ability of endothelial cell tube formation and migration. Placenta-derived exosome–treated macrophages had no impact on T-cell proliferation. Together, we demonstrated that placenta-derived exosomes polarize macrophages to acquire a decidua-like macrophage phenotype to modulate trophoblast and endothelial cell functions.