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

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.