IL-18 produced by pregnant uterus promotes essential inflammatory responses and fetoplacental growth. Ino et al.

[Summery] Placental insufficiency affects fetomaternal health throughout life. Although the interaction between the maternal uterine immune milieu and fetal-derived cells plays a crucial role in placental formation, several aspects remain unclear. Therefore, we conducted this study to investigate the effects of interleukin (IL)-18, a distinctive cytokine with both proinflammatory and anti-inflammatory properties, on the uterine immune milieu and placental development. Our results identified pregnant uterine smooth muscle cells as an important source of IL-18, which supports homeostatic type 1 immune responses. IL-18 facilitates appropriate placental development through uterine vascular remodeling and placental angiogenesis. Smooth muscle cell–specific Il18-knockout dam mice exhibited excessive cytotoxicity of uterine NK cells, impaired fetoplacental growth, and elevated maternal blood pressure, reflecting preeclampsia-like phenotypes. Their offspring demonstrated a tendency toward excessive weight gain and delayed neurodevelopment. Overall, this study emphasizes the essential role of IL-18 in placental formation and its wider implications for fetomaternal health. [Deposited dataset] We have deposited the raw, uncropped Western blot data prior to cropping. Each .zip archive is labeled to match the corresponding figure name in the manuscript. -Ino_et_al_Figure1.zip --1A_NLRP3_WB.tiff --1A_GAPDH_WB.tiff --1A_Caspase1_WB.tiff --1A_IL-18_WB.tiff --1A_Summery_WB.tif -Ino_et_al_FigureS1.zip --S1A_Caspase11_WB.tiff --S1A_GasderminD_WB.tiff --S1A_Caspase8_WB.tiff --S1A_GAPDH_WB.tiff --S1A_Summery_WB.tif[Summery] 胎盘功能不全可终身影响母婴健康。尽管母体子宫免疫微环境与胎儿来源细胞间的相互作用在胎盘形成中发挥关键作用，但仍有诸多方面尚未明确。为此，本研究旨在探讨兼具促炎与抗炎双重特性的独特细胞因子——白细胞介素（interleukin，IL）-18对子宫免疫微环境与胎盘发育的影响。本研究结果证实，妊娠子宫平滑肌细胞是IL-18的重要来源，可维持稳态1型免疫应答。IL-18可通过子宫血管重塑与胎盘血管生成，促进胎盘正常发育。子宫平滑肌细胞特异性IL-18基因敲除母鼠表现出子宫自然杀伤（natural killer, NK）细胞毒性过度、胎儿胎盘生长受损以及母体血压升高，呈现子痫前期样表型。其子代出现体重过度增加与神经发育延迟的倾向。综上，本研究明确了IL-18在胎盘形成中的核心作用，及其对母婴健康的广泛影响。 [Deposited dataset] 我们已上传原始未裁切的蛋白免疫印迹（Western blot）数据。每个压缩包均以对应稿件中的图表名称命名。 -Ino_et_al_Figure1.zip --1A_NLRP3_WB.tiff --1A_GAPDH_WB.tiff --1A_Caspase1_WB.tiff --1A_IL-18_WB.tiff --1A_Summery_WB.tif -Ino_et_al_FigureS1.zip --S1A_Caspase11_WB.tiff --S1A_GasderminD_WB.tiff --S1A_Caspase8_WB.tiff --S1A_GAPDH_WB.tiff --S1A_Summery_WB.tif