Deletion of ACLY Disrupts Histone Acetylation and IL-10 Secretion in Trophoblasts, Which Inhibits M2 Polarization of Macrophages: A Possible Role in Recurrent Spontaneous Abortion

Abstract

Changes to macrophage polarization affect the local microenvironment of the placenta, resulting in pathological pregnancy diseases such as recurrent spontaneous abortion (RSA). Macrophages are in close contact with trophoblasts during placental development, and trophoblast-derived cytokines are important regulators of macrophage polarization and function. Histone acetylation can affect the expression and secretion of cytokines, and ATP citrate lyase (ACLY) is an important factor that regulates histone acetylation. The aim of this study was to investigate the effect of ACLY expression differences in trophoblast on macrophage polarization and its mechanism. Our data demonstrate that ACLY level in placental villi of patients with RSA is decreased, which may lead to the inhibition of histone acetylation in trophoblasts, thereby reducing the secretion of IL-10. Reduced IL-10 secretion activates endoplasmic reticulum stress in macrophages, thus inhibiting their M2 polarization.

Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data

“…To further systematically understand the immunomodulatory activities that decidua-DEGs and placenta-DEGs were involved in, we performed immune function enrichment analysis by CluGO, which displayed that these DEGs were mainly closely related to macrophage activity, such as affecting macrophage tolerance induction, regulation of macrophage antigen processing and presentation as well as macrophage activation. It has been confirmed that DSC-conditioned medium (CM) can promote macrophage survival and induce typical phenotype of decidual macrophages, and that DSC-CM also inhibit the proinflammatory effects of granulocyte-macrophage colony- (43). From the above studies we could project that DSCs and trophoblasts exerted significant effects on the phenotype and function of decidual macrophage.…”

“…Chen et al. discovered that reduced IL-10 derived from placental villi of URSA patients could activate endoplasmic reticulum stress of macrophages, thereby inhibiting M2 polarization ( 43 ). From the above studies we could project that DSCs and trophoblasts exerted significant effects on the phenotype and function of decidual macrophage.…”