Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development

• DOI: 10.1016/j.xcrm.2024.101476
• Publication Date: 2024-03-21T11:24:44Z
• Authors: Jinghe Zhang; Weidong Zhao; Yonggang Zhou; Shengdi Xi; Xiuxiu Xu; Xianghui Du; Xiaohu Zheng; Weiping Hu; Rui Sun; Zhigang Tian; Binqing Fu; Haiming Wei
• Keywords: Inflammation; Mice; Interleukin-16; T-Lymphocytes; Endometriosis; Pyroptosis; Animals; Humans; Female; Article

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.