Decidualized endometrial stromal cells are capable of driving M2 macrophage differentiation

Abstract

During decidualization, the recruited monocytes in the endometrium would undergo M2 macrophage differentiation with an immunosuppressive phenotype. Inappropriate macrophage differentiation is associated with miscarriage and preeclampsia. However, the regulations of the macrophages differentiation in the endometrium is unclear. In this study, we want to explore whether the macrophage differentiation could be regulated by decidualized endometrial stromal cells. hTERT-immortalized human endometrial stromal cells (T-HESCs) were treated with medroxyprogesterone acetate (MPA) and 8-bromo-cAMP to induce decidualization. Human monocytic cell line THP-1 cells primed with phorbol 12-myristate 13-acetate (PMA) or peripheral blood monocytes were cultured in the conditioned medium of decidualized T-HESCs (D(+)CM) or non-decidualized T-HESCs (D(-)CM) to induce macrophage differentiation. The macrophage differentiation of PMA-primed THP-1 (pTHP-1) or monocytes induced by D(+)CM or D(-)CM were evaluated by detecting the expressions of CD markers and cytokines using flowcytometry and ELISA, respectively. The effects of the CM-treated pTHP-1 on the decidualization of T-HESCs and the invasion of HTR-8 trophoblast cells were evaluated. The differences between groups were analyzed using the Student t test. D(+)CM-treated pTHP-1 or D(+)CM-treated monocytes had a M2 differentiation with downregulations of CD11c, IL-1β, and TNF-α, and upregulations of CD163, IL-10, and TGF-β, compared with that of D(-)CM-treated cells. D(+)CM-treated pTHP-1 could maintain the decidualization of T-HESCs and promote the cell invasion of HTR-8 compared with D(-)CM-treated pTHP-1. The secretion of decidualized endometrial stromal cells could induce a M2 macrophage differentiation that may help the maintenance of decidualization and the development of placenta in vivo.