Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development
Jinghe Zhang, Weidong Zhao, Yonggang Zhou, Shengdi Xi, Xiuxiu Xu, Xianghui Du, Xiaohu Zheng, Weiping Hu, Rui Sun, Zhigang Tian, Binqing Fu, Haiming Wei
Abstract
Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.