Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Department of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Front Immunol. 2023 Jan 6;13:1047986. doi: 10.3389/fimmu.2022.1047986. eCollection 2022.
Preeclampsia (PE) is a severe placenta-related pregnancy disease that has been associated with maternal systemic inflammation and immune system disorders. However, the distribution and functional changes in immune cells of the maternal-placental interface have not been well characterized. Herein, cytometry by time-of-flight mass spectrometry (CyTOF) was used to investigate the immune atlas at the decidua, which was obtained from four PE patients and four healthy controls. Six superclusters were identified, namely, T cells, B cells, natural killer (NK) cells, monocytes, granulocytes, and others. B cells were significantly decreased in the PE group, among which the reduction in CD27+CD38+ regulatory B cell (Breg)-like cells may stimulate immune activation in PE. The significantly increased migration of B cells could be linked to the significantly overexpressed chemokine C-X-C receptor 5 (CXCR5) in the PE group, which may result in the production of excessive autoantibodies and the pathogenesis of PE. A subset of T cells, CD11c+CD8+ T cells, was significantly decreased in PE and might lead to sustained immune activation in PE patients. NK cells were ultimately separated into four subsets. The significant reduction in a novel subset of NK cells (CD56-CD49a-CD38+) in PE might have led to the failure to suppress inflammation at the maternal-fetal interface during PE progression. Moreover, the expression levels of functional markers were significantly altered in the PE group, which also inferred that shifts in the decidual immune state contributed to the development of PE and might serve as potential treatment targets. This is a worthy attempt to elaborate the differences in the phenotype and function of CD45+ immune cells in the decidua between PE and healthy pregnancies by CyTOF, which contributes to understand the pathogenesis of PE, and the altered cell subsets and markers may inspire the immune modulatory therapy for PE.
子痫前期 (PE) 是一种严重的胎盘相关妊娠疾病，与母体全身炎症和免疫系统紊乱有关。然而，母体胎盘界面免疫细胞的分布和功能变化尚不清楚。在此，我们使用时间飞行质谱流式细胞术 (CyTOF) 分析了来自 4 名 PE 患者和 4 名健康对照者的蜕膜免疫图谱。鉴定出了 6 个超级簇，分别是 T 细胞、B 细胞、自然杀伤 (NK) 细胞、单核细胞、粒细胞和其他细胞。PE 组 B 细胞显著减少，其中 CD27+CD38+调节性 B 细胞 (Breg)样细胞的减少可能刺激 PE 中的免疫激活。B 细胞的显著迁移可能与 PE 组中趋化因子 C-X-C 受体 5 (CXCR5) 的显著过表达有关，这可能导致过度产生自身抗体和发生 PE。PE 患者中，一组显著减少的 CD11c+CD8+T 细胞可能导致持续的免疫激活。NK 细胞最终分为四个亚群。PE 中一种新型 NK 细胞 (CD56-CD49a-CD38+) 的显著减少可能导致在 PE 进展过程中母体胎儿界面的炎症抑制失败。此外，PE 组中功能标志物的表达水平显著改变，这也推断出蜕膜免疫状态的改变导致了 PE 的发生，并且可能成为潜在的治疗靶点。这是通过 CyTOF 详细阐述 PE 和健康妊娠蜕膜中 CD45+免疫细胞表型和功能差异的一次有价值的尝试，有助于理解 PE 的发病机制，改变的细胞亚群和标志物可能为 PE 的免疫调节治疗提供启示。
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