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

Published: 12 December 2025| Version 1 | DOI: 10.17632/sh48gkj9sc.1
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[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

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Before western blotting, after flash-freezing each tissue in liquid nitrogen and crushing it, the samples were lysed in a sample buffer containing 50 mM HEPES/KOH (Nacalai Tesque, #15639-84), 250 mM NaCl, 1.5 M MgCl₂ (Nacalai Tesque, #20909-42), 1 mM EDTA (Nacalai Tesque, #06894-14), 1 mM EGTA (Nacalai Tesque, #08907-42), and 0.5% Nonidet P-40 (Sigma-Aldrich, #N-6507). Whole-cell lysates were subjected to SDS-PAGE under reducing conditions and transferred onto polyvinylidene fluoride membranes. After blocking, the membranes were incubated with a monoclonal antibody. Next, they were treated with horseradish peroxidase–conjugated secondary antibodies, and then visualized using Chemi-Lumi One Super (Nacalai Tesque, #02230-30) together with LiminoGraph Ⅰ (ATTO Corporation, #P1ATO1000004-1), according to the manufacturers’ instructions. Antibodies used in the western blotting are listed in the key resources table. Band densities were quantified using ImageJ (https://imagej.net/ij/).

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