Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
Sci Rep. 2021 Mar 25;11(1):6870. doi: 10.1038/s41598-021-86390-0.
Despite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal-fetal interface, using clinical samples and animal models. In this study, we found that the infiltration of NETs and dNKs, especially CD56CD16 NK cells, was significantly increased in pregnant individuals with SLE with placental insufficiency. In the murine models of SLE, the number of dNKs was significantly decreased due to the decreased formation of NETs affected by Ly6G. Moreover, the histopathological placental injury was reduced, with a remarkable increase in fetal birth weight. This study shows that NETs may contribute to immunological disorder in the placenta and the pathological changes in pregnancies with SLE, which provides a research basis for further explorations of the mechanism of SLE in placental impairment.
尽管在系统性红斑狼疮（SLE）女性妊娠管理方面取得了进展，但不良妊娠结局的发生率仍高于普通人群。近年来，中性粒细胞胞外诱捕网（NETs）已被证明在自身免疫性疾病和胎盘损伤中均具有危害性。我们研究了是否可以在 SLE 孕妇的胎盘组织中检测到 NETs，并使用临床样本和动物模型探讨了 NETs 与构成母体-胎儿界面中大多数免疫细胞的蜕膜自然杀伤细胞（dNK）之间的关系。在这项研究中，我们发现，在存在胎盘功能不全的 SLE 孕妇中，NETs 和 dNKs（尤其是 CD56CD16 NK 细胞）的浸润显著增加。在 SLE 小鼠模型中，由于 Ly6G 影响 NETs 的形成而减少，dNK 细胞的数量明显减少。此外，组织病理学上的胎盘损伤减轻，胎儿出生体重显著增加。这项研究表明，NETs 可能导致 SLE 孕妇胎盘免疫失调和病理变化，为进一步探讨 SLE 在胎盘损伤中的机制提供了研究基础。
