Modulators of the Balance between M1 and M2 Macrophages during Pregnancy

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.

MicroRNA‐transcriptome networks in whole blood and monocytes of women undergoing preterm labour

“…The target genes of the miRNAs differentially expressed within monocytes were enriched for a total of 19 GO gene sets including those related to interleukin production and activation of the immune system, such as ‘regulation of interleukin production’ (Interleukins 2, 4 and 6), as well as T cell, lymphocyte and monocyte proliferation. The monocyte population expands during pregnancy and differentiates into a pro‐inflammatory phenotype during labour . Our work indicates that part of this expansion in monocytes may be transcriptionally regulated by a subset of miRNAs in monocytes.…”

Macrophage targeting: opening new possibilities for cancer immunotherapy

“…It is now widely accepted that plasticity is a hallmark of macrophages. For example, macrophages cultured with interleukin‐4 (IL‐4) and IL‐13 (called alternatively activated macrophages) produce anti‐inflammatory cytokines such as IL‐10 and transforming growth factor‐ β (TGF‐ β ) that can inhibit CD8 + T‐cell functions, whereas macrophages cultured with lipopolysaccharide and interferon‐ γ (called classically activated macrophages) secrete pro‐inflammatory cytokines such as tumour necrosis factor‐ α (TNF‐ α ) and IL‐1 β . Furthermore, alternatively activated macrophages can change their phenotype to classically activated macrophages when they are exposed to interferon‐ γ and lipopolysaccharide .…”

“…For example, macrophages cultured with interleukin-4 (IL-4) and IL-13 (called alternatively activated macrophages) produce anti-inflammatory cytokines such as IL-10 and transforming growth factor-b (TGF-b) that can inhibit CD8 + T-cell functions, whereas macrophages cultured with lipopolysaccharide and interferon-c (called classically activated macrophages) secrete pro-inflammatory cytokines such as tumour necrosis factor-a (TNF-a) and IL-1b. 28 Furthermore, alternatively activated macrophages can change their phenotype to classically activated macrophages when they are exposed to interferon-c and lipopolysaccharide. 29 As alternatively but not classically activated macrophages suppress in vitro T-cell proliferation, 30 these in vitro studies suggest that targeting macrophage differentiation signals can reprogram TAM from immune suppressive to supportive cells and thereby enhance antitumour immune reactions induced by immunotherapy.…”

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies

“…For successful pregnancy, there must be a delicate balance of immune tolerance at the maternal‐fetal interface, which is mediated by unique DICs . Decidual macrophages are a heterogenous population with different phenotypes that contribute to adaptive responses to the complex environment at the maternal‐fetal interface . Houser et al have demonstrated that decidual macrophages do not fit into either of the M1 or the M2 subsets.…”

“…67 Decidual macrophages are a heterogenous population with different phenotypes that contribute to adaptive responses to the complex environment at the maternal-fetal interface. 68 Houser et al 69 have demonstrated that decidual macrophages do not fit into either of the M1 or the M2 subsets. However, certain studies have shown that decidual macrophages, which fulfill an important role in the endometrium during pregnancy, are more closely related to the M2 phenotype.…”