Inhibition of pregnancy-associated granulocytic myeloid-derived suppressor cell expansion and arginase-1 production in preeclampsia

Abstract

Myeloid-derived suppressor cells (MDSCs) expand in maternal peripheral blood and cord blood during normal pregnancy to maintain maternal-fetal tolerance. Here we investigated the expansion and function of MDSCs in preeclampsia (PE) patients. Maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs) were sampled from healthy pregnant women and PE patients, and analyzed for the frequencies and phenotypes of MDSCs and T cells. Serum levels of key human MDSC effector enzymes were measured using appropriate detection kits. Peripheral blood samples of healthy non-pregnant women were used as controls. We found that normal pregnancy is associated with a significant increase of immunosuppressive MDSCs and regulatory T (Treg) cells. There was no significant difference in the frequency of Treg cells between normal pregnancies and PE patients, but the pregnancy-associated increase of granulocytic MDSCs (G-MDSCs), but not monocytic MDSCs (M-MDSCs), in both PBMCs and CBMCs was markedly inhibited in PE patients. Furthermore, serum levels of Arg-1, an important effector molecule for G-MDSC were significantly reduced in PE patients compared to healthy pregnant women. In conclusion, the lack of G-MDSC expansion is a most notable feature of PE-associated immune-cell alterations, suggesting that restoring G-MDSCs may have the potential to treat PE.

Keywords: Myeloid derived suppressor cells; Preeclampsia; Reproductive immunology; Tolerance; arginase-1.