Trophoblast secretion of leukemia inhibitory factor (LIF) regulates macrophage immunoinhibitory function 4471

Abstract Description Macrophages are the most abundant immune cell of the placenta and have been implicated in the pathogenesis of pregnancy complications.We generated placental-conditioned macrophages using conditioned media from human placental chorionic villi explants and exposing these to THP-1 cells to investigate how the placenta can influence macrophage function. Placental conditioned macrophages were characterized by functional assays (cell migration, phagocytosis), RNA sequencing and cytokine profiling. Placental conditioned macrophages produced abundant IL-10, had gene activation in immune and wound healing pathways and suppressed phagocytosis. Macrophages migrate towards conditioned media in transwell models and placental conditioned macrophages facilitate trophoblast wound healing by scratch assay. Luminex profiling identified soluble gp130 and LIF as abundant in chrorionic villi conditioned media and correlated with IL-10 production by placental conditioned macrophages. LIF localized to the syncytiotrophoblast layer in chorionic villi and using an interfering antibody to LIF, we were able to reduce IL-10 production by placental conditioned macrophages. Inhibition of jak/stat signaling downstream of LIF also resulted in reduced IL-10 production and SOCS3 activation. Additionally, purified LIF facilitated macrophage migration and suppressed phagocytosis. In conclusion, LIF secretion by trophoblasts leads to macrophage migration and suppression of phagocytosis with activation of immun Funding Sources NIH K12 00849 Topic Categories Mucosal and Regional Immunology (MUC)