The role of smooth muscle cell-derived IL-18 in uterine immune milieu and fetoplacental growth

There is a close relationship between pregnancy and immune responses. For example, an anti-inflammatory state is essential for maintaining pregnancy by promoting maternal tolerance toward the semi-allogeneic fetus, whereas pro-inflammatory conditions are crucial for processes such as maternal tissue remodeling during embryo implantation and the induction of labor. Increasing evidence suggests that various cell types within the uteroplacental immune environment contribute to these immune responses, and immunological approaches have been employed to investigate the pathophysiology and potential treatments of pregnancy-related complications. Interleukin-18 (IL-18) is a unique cytokine with both pro-inflammatory and anti-inflammatory properties; however, its roles during pregnancy remain largely unclear. We have found that smooth muscle cells (SMCs) in the uterine myometrium are an important source of IL-18, and that the homeostatic production of IL-18 promotes fetal development by supporting maternal uterine remodeling and placental growth. To further investigate the effects of IL-18 on the uterine immune milieu, we established SMC-specific Il18 conditional knockout (cKO) mice and performed RNA sequencing of uterine immune cells.