PD-1/PD-L1 信号通路调节蜕膜巨噬细胞极化，并可能参与子痫前期的发生。
The PD-1 /PD-L1 signaling pathway regulates decidual macrophage polarization and may participate in preeclampsia.
机构信息
Department of Obstetrics and Gynecology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan 250001, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250001, China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250001, China.
出版信息
J Reprod Immunol. 2024 Aug;164:104258. doi: 10.1016/j.jri.2024.104258. Epub 2024 May 16.
The pathogenesis of preeclampsia (PE) has not been elucidated, but immune imbalance is known to be one of the main pathogeneses. Dysfunction of decidual macrophages can lead to PE, and the PD-1/PD-L1 signaling pathway is associated with macrophage polarization. However, the relationship between the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization and the onset of PE has not been fully elucidated. In this study, we analyzed the expression of CD68, iNOS, CD206, PD-1 and PD-L1 and the coexpression of CD68PD-1 and CD68PD-L1 in the decidual tissue of PE patients (n= 18) and healthy pregnant women (n=20). We found that CD68 and iNOS expression was increased in the decidua of PE patients (P < 0.001) and that CD206, PD-1 and PD-L1 expression and CD68PD-1 and CD68PD-L1 coexpression were decreased (P < 0.001). To assess the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization, we added an anti-PD-1 mAb (pembrolizumab) or an anti-PD-L1 mAb (durvalumab) during THP-1 differentiation into M1 macrophages. Then, we detected the polarization of CD68CD80 macrophages and the expression of iNOS. To examine the effect of macrophage polarization on the invasion ability of trophoblast cells, macrophages were cocultured with HTR8/SVneo cells, and the invasion ability of HTR8/SVneo cells was detected via transwell assays. We found that CD68CD80 macrophage polarization was enhanced (P<0.05) and that iNOS expression was greater (P<0.01) in the pembrolizumab group. In the durvalumab group, CD68CD80 macrophage polarization and iNOS expression were also increased (P<0.05 and P<0.001). Compared with that in the untreated group, the aggressiveness of HTR8/SVneo cells was decreased in both the pembrolizumab group (P < 0.01) and the durvalumab group (P < 0.001). These findings indicate that the PD-1/PD-L1 signaling pathway may play an important role in the pathogenesis of PE by influencing macrophage polarization and reducing the invasion ability of trophoblasts.
子痫前期（PE）的发病机制尚未阐明，但已知免疫失衡是主要发病机制之一。蜕膜巨噬细胞功能障碍可导致 PE，而 PD-1/PD-L1 信号通路与巨噬细胞极化有关。然而，PD-1/PD-L1 信号通路对巨噬细胞极化和 PE 发病的影响之间的关系尚未完全阐明。在这项研究中，我们分析了 CD68、iNOS、CD206、PD-1 和 PD-L1 的表达以及 CD68PD-1 和 CD68PD-L1 在 PE 患者（n=18）和健康孕妇（n=20）的蜕膜组织中的共表达。我们发现，PE 患者的蜕膜中 CD68 和 iNOS 的表达增加（P<0.001），而 CD206、PD-1 和 PD-L1 的表达以及 CD68PD-1 和 CD68PD-L1 的共表达降低（P<0.001）。为了评估 PD-1/PD-L1 信号通路对巨噬细胞极化的影响，我们在 THP-1 分化为 M1 巨噬细胞的过程中添加了抗 PD-1 mAb（pembrolizumab）或抗 PD-L1 mAb（durvalumab）。然后，我们检测了 CD68CD80 巨噬细胞的极化和 iNOS 的表达。为了研究巨噬细胞极化对滋养层细胞侵袭能力的影响，将巨噬细胞与 HTR8/SVneo 细胞共培养，并通过 Transwell 实验检测 HTR8/SVneo 细胞的侵袭能力。我们发现，pembrolizumab 组 CD68CD80 巨噬细胞的极化增强（P<0.05），iNOS 的表达增加（P<0.01）。在 durvalumab 组，CD68CD80 巨噬细胞的极化和 iNOS 的表达也增加（P<0.05 和 P<0.001）。与未处理组相比，pembrolizumab 组（P<0.01）和 durvalumab 组（P<0.001）中 HTR8/SVneo 细胞的侵袭能力降低。这些发现表明，PD-1/PD-L1 信号通路可能通过影响巨噬细胞极化和降低滋养层细胞的侵袭能力在 PE 的发病机制中发挥重要作用。
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