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-β 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.

巨噬细胞是蜕膜微环境的主要组成部分，在人类植入和胎盘的形成中起着重要作用。据报道滋养细胞迁移到子宫内膜并与蜕膜细胞相互作用，参与巨噬细胞的极化。然而，滋养细胞调节M2巨噬细胞极化的潜在机制仍需进一步探索。在这里，我们使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，巨噬细胞倾向于极化为M2亚型，并伴随着多个M2标记物的表达增加，包括CD206和CCL18 mRNA表达以及IL-10和TGF-β蛋白水平。进一步的实验确定，滋养层来源的IL-6是主要的贡献者，通过激活Stat3途径促进M2巨噬细胞极化。此外，活化的M2巨噬细胞以反馈的方式在滋养细胞的侵袭和迁移中发挥促进作用。临床上，来自组织学的结果表明，正常妊娠患者胎盘绒毛组织中的IL-6表达与蜕膜中CD206阳性巨噬细胞浸润呈正相关。总之，我们的发现表明，滋养层细胞通过IL-6 / Stat3信号通路诱导M2巨噬细胞极化，进而促进滋养层细胞的侵袭和迁移。这些结果为正常妊娠母婴微环境中巨噬细胞与滋养细胞之间的串扰提供了见解。活化的M2巨噬细胞以反馈方式在滋养细胞的侵袭和迁移中发挥促进作用。临床上，来自组织学的结果表明，正常妊娠患者胎盘绒毛组织中的IL-6表达与蜕膜中CD206阳性巨噬细胞浸润呈正相关。总之，我们的发现表明，滋养层细胞通过IL-6 / Stat3信号通路诱导M2巨噬细胞极化，进而促进滋养层细胞的侵袭和迁移。这些结果为正常妊娠母婴微环境中巨噬细胞与滋养细胞之间的串扰提供了见解。活化的M2巨噬细胞以反馈方式在滋养细胞的侵袭和迁移中发挥促进作用。临床上，来自组织学的结果表明，在正常妊娠患者中，胎盘绒毛组织中的IL-6表达与蜕膜中CD206阳性巨噬细胞浸润呈正相关。总之，我们的发现表明，滋养层细胞通过IL-6 / Stat3信号通路诱导M2巨噬细胞极化，进而促进滋养层细胞的侵袭和迁移。这些结果为正常妊娠母婴微环境中巨噬细胞与滋养细胞之间的串扰提供了见解。组织学结果表明，正常妊娠患者胎盘绒毛组织中的IL-6表达与蜕膜CD206阳性巨噬细胞浸润呈正相关。总之，我们的发现表明，滋养层细胞通过IL-6 / Stat3信号通路诱导M2巨噬细胞极化，进而促进滋养层细胞的侵袭和迁移。这些结果为正常妊娠母婴微环境中巨噬细胞与滋养细胞之间的串扰提供了见解。组织学结果表明，正常妊娠患者胎盘绒毛组织中的IL-6表达与蜕膜CD206阳性巨噬细胞浸润呈正相关。总之，我们的发现表明，滋养层细胞通过IL-6 / Stat3信号通路诱导M2巨噬细胞极化，进而促进滋养层细胞的侵袭和迁移。这些结果为正常妊娠母婴微环境中巨噬细胞与滋养细胞之间的串扰提供了见解。