Disordered IL-33/ST2 Activation in Decidualizing Stromal Cells Prolongs Uterine Receptivity in Women with Recurrent Pregnancy Loss

摘要: Decidualization renders the endometrium transiently receptive to an implanting blastocyst although underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting profound anti-inflammatory response includes downregulation increased expression soluble decoy sST2. We demonstrate secrete factors permissive embryo implantation in mice only during phase decidual process. knockdown undifferentiated was sufficient abrogate this response. Further, sequential activation IL-33/ST2L/sST2 axis disordered decidualizing from women with recurrent pregnancy loss. Signals these cultures prolonged window but also caused subsequent failure mice. Thus, Il-33/ST2 HESCS drives autoinflammatory controls temporal receptivity genes. Failure constrain predisposes miscarriage by allowing out-of-phase unsupportive uterine environment.