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

ACLY 缺失会破坏滋养细胞中的组蛋白乙酰化和 IL-10 分泌,从而抑制巨噬细胞的 M2 极化:可能在复发性自然流产中发挥作用

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作者:Xin Chen, Qian Lin Song, Ze Hong Li, Rui Ji, Jia Yu Wang, Chang Ge, Zhuo Ni Xiao, Duan Ying Guo, Jing Yang

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.

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