Human placental exosomes induce maternal systemic immune tolerance in a monocyte-dependent manner

Maternal immune tolerance toward to the semi-allograft fetus is a prerequisite condition for successful pregnancy. However, the role of maternal monocytes in the induction of systemic immune tolerance is poorly understood. Here we report that placenta facilitates maternal immune tolerance by extruding exosomes. Maternal monocytes were transformed into an immunosuppressive phenotype after taking up exosomes. Mechanistically, PD-L1 was significantly increased in pEXO-educated monocytes via miRNA-29a-3p/PTEN signaling pathway. In addition, pEXO-treated monocytes could increase Treg pool in maternal blood through a direct cell-cell interaction. Moreover, Th1 cytokines, IFN? and TNF-a, in monocyte-T cell co-culture system were significantly decreased. Together, our results indicated that maternal monocyte is indispensable components in systemic immune tolerance establishment. Overall design: mRNA profiles of pEXO-treated monocyte (N=4) and Control monocyte (N=4)