Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization
Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization
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滋养层来源的 IL-6 通过激活 Stat3 介导的 M2 巨噬细胞极化，成为正常妊娠的重要因素
DOI：
10.1016/j.intimp.2020.106788
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发表时间：
2021-01-12
影响因子：
5.6
通讯作者：
Yang, Jing
中科院分区：
文献类型：
--
作者：
Ding, Jinli;Yang, Chaogang;Yang, Jing
大颗粒细胞是蜕膜微环境的主要组成部分，在人类着床和胎盘形成中起重要作用。据报道，迁移到子宫内膜并与蜕膜细胞相互作用的滋养细胞参与巨噬细胞的极化。然而，滋养层细胞调节M2巨噬细胞极化的可能机制仍需进一步探讨。在此，我们采用共培养模型来研究巨噬细胞和滋养细胞之间的相互作用。我们的结果表明，当与滋养层细胞共培养时，巨噬细胞倾向于向M2亚型转化，伴随着多种M2标志物的表达增加，包括CD 206和CCL 18 mRNA表达以及IL-10和TGF-β蛋白水平。进一步的实验表明，滋养层来源的IL-6，作为主要贡献者，通过激活Stat 3途径促进M2巨噬细胞极化。活化的M2巨噬细胞以反馈方式促进滋养细胞的侵袭和迁移。临床上，组织学结果显示，正常妊娠患者胎盘绒毛组织中IL-6的表达与蜕膜中CD 206阳性巨噬细胞的浸润呈正相关。总而言之，我们的研究结果表明滋养层细胞通过IL-6/Stat 3信号途径诱导M2巨噬细胞极化，从而促进滋养层细胞的侵袭和迁移。这些结果为了解正常妊娠中母胎微环境中巨噬细胞和滋养层细胞之间的相互作用提供了依据。
Macrophages are major components of decidual microenvironment that play an important role in human implantation and placentation. Trophoblasts which migrate into the endometrium and interplay with decidual cells, have been reported to participate in the polarization of macrophages. However, the potential mechanisms of trophoblasts modulating M2 macrophages polarization still need further exploration. Herein, we used the co cultured model to investigate the interaction between macrophages and trophoblasts. Our results illustrated that when co-cultured with trophoblasts, macrophages tended to polarize to M2-subtype, accompanied by increased expression of multiple M2 markers including CD206 and CCL18 mRNA expression and IL-10 and TGF-beta protein level. Further experiments identified that trophoblast-derived IL-6, as the major contributor, promoted M2 macrophages polarization by activating Stat3 pathway. Moreover, activated M2 macrophages exerted a promoting role in the invasion and migration of trophoblasts in a feedback manner. Clinically, results from histology demonstrated that IL-6 expression in placental villous tissues was positive correlated with CD206-positive macrophage infiltration in decidua in normal pregnancy patients. Altogether, our findings indicate that trophoblasts induce M2 macrophages polarization via IL-6/Stat3 signal pathway, which in turn promote the invasion and migration of trophoblasts. These results provide insights into the crosstalk between macrophages and trophoblasts at maternal-fetal microenvironment in normal pregnancy.