Abstract
Macrophages are a subset of mononuclear phagocytes of the innate immune system with high plasticity and heterogeneity. At the maternal–fetal interface, macrophages are present in all stages of pregnancy and involved in a variety of activities, including regulation of immune cell activities, decidualization, placental cell invasion, angiogenesis, parturition, and postpartum uterine involution. The activation state and function of uterine–placental macrophages are largely dependent on the local tissue microenvironment. However, disruption of the uterine microenvironment can have profound effects on macrophage activity and subsequently impact pregnancy outcome. Thus, appropriately and timely regulated macrophage polarization has been considered a key determinant of successful pregnancy. Targeting macrophage polarization might be an efficient strategy for maintaining maternal–fetal immune homeostasis and a normal pregnancy. Here, we will review the latest findings regarding the modulators regulating macrophage polarization in healthy pregnancies and pregnancy complications, which might provide a basis for macrophage-centered therapeutic strategies.
Highlights
During pregnancy, the maternal immune system is greatly challenged by the semiallogeneic fetus
No intrinsic impairment of human amniotic mesenchymal stem/stromal cell (MSC) (hAMSC) was found between healthy pregnancy and PE [108]. These results suggest that hAMSCs might not contribute to the development of PE but could participate in offsetting the inflammatory status that characterizes PE
This accumulation elicits local immune responses, leading to the abrogation of tolerance at the maternal–fetal interface and fetal rejection. All these findings suggest that T-cell immunoglobulin and mucin domain protein 3 (Tim-3) blockade during the first trimester skews macrophages toward M1 activation rather than M2 polarization
Summary
Macrophages are a subset of mononuclear phagocytes of the innate immune system with high plasticity and heterogeneity. At the maternal–fetal interface, macrophages are present in all stages of pregnancy and involved in a variety of activities, including regulation of immune cell activities, decidualization, placental cell invasion, angiogenesis, parturition, and postpartum uterine involution. The activation state and function of uterine–placental macrophages are largely dependent on the local tissue microenvironment. Disruption of the uterine microenvironment can have profound effects on macrophage activity and subsequently impact pregnancy outcome. Appropriately and timely regulated macrophage polarization has been considered a key determinant of successful pregnancy. Targeting macrophage polarization might be an efficient strategy for maintaining maternal–fetal immune homeostasis and a normal pregnancy. We will review the latest findings regarding the modulators regulating macrophage polarization in healthy pregnancies and pregnancy complications, which might provide a basis for macrophage-centered therapeutic strategies
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