Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, Detroit, Michigan, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
J Leukoc Biol. 2022 Jan;111(1):237-260. doi: 10.1002/JLB.5RU1120-787RR. Epub 2021 Apr 13.
Preeclampsia, defined as new-onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi-systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti-angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal-fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.
子痫前期是指在妊娠 20 周或以后新出现的高血压并伴有蛋白尿的疾病，是全球围产期发病率和死亡率的主要原因。这种主要的多系统综合征的病理生理学包括胎盘着床缺陷、氧化应激、内皮功能障碍、存在抗血管生成状态和血管内炎症等。在这篇综述中，我们全面概述了与子痫前期发病机制相关的细胞免疫反应。具体来说，我们总结了先天和适应性免疫细胞在受这种妊娠并发症影响的女性的母体循环、生殖组织和母体-胎儿界面中的作用。与子痫前期发病机制相关的主要细胞亚群包括调节性 T 细胞、效应 T 细胞、NK 细胞、单核细胞、巨噬细胞和中性粒细胞。我们还总结了关于在这种临床情况下特征不太明显的免疫细胞的文献，如 γδ T 细胞、固有自然杀伤 T 细胞、树突状细胞、肥大细胞和 B 细胞。此外，我们讨论了利用各种子痫前期动物模型进行的体内研究，以进一步支持免疫细胞在这种疾病中的作用。最后，我们强调了子痫前期免疫生物学中需要进一步研究的现有知识空白。本综述的目的是促进转化研究，从而提出临床相关的策略，改善由子痫前期产科综合征引起的不良围产期结局。
