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

Zhang, Jinghe; Zhao, Weidong; Zhou, Yonggang; Xi, Shengdi; Xu, Xiuxiu; Du, Xianghui; Zheng, Xiaohu; Hu, Weiping et al. · Cell Rep Med · 2024

basic_science · Level V

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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.

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