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

Pregnancy involves a wide range of adaptations in the maternal body. Maternal immune tolerance towards 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 (pEXO) are small vesicles carrying active biological molecules such as miRNAs, proteins, and lipids. The pEXO have been implicated in endothelial cell activation, smooth muscle cell migration, and T cell apoptosis, but it is unknown whether pEXO would affect the development and functions of decidual macrophages. In this study, we reported that pEXO stimulated macrophage polarization into alternatively activated (M2)-macrophages. Mechanistically, miRNA-30d-5p from the pEXO induced macrophage polarization to M2 phenotype by targeting histone deacetylase 9 (HDAC9). Furthermore, the conditioned medium of pEXO-treated macrophages promoted trophoblast migration and invasion. By contrast, the conditioned medium impaired the ability of endothelial cell tube formation and migration. pEXO-treated macrophages had no impact on T cell proliferation. Together, we demonstrated that pEXO polarize macrophage to acquire a decidua-like macrophage phenotype to modulate trophoblast and endothelial cell functions.