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

doi:10.1016/j.xcrm.2024.101476

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

Cell Rep Med. 2024 Mar 19;5(3):101476. doi: 10.1016/j.xcrm.2024.101476.

Authors

Jinghe Zhang¹, Weidong Zhao², Yonggang Zhou¹, Shengdi Xi¹, Xiuxiu Xu¹, Xianghui Du¹, Xiaohu Zheng¹, Weiping Hu³, Rui Sun¹, Zhigang Tian¹, Binqing Fu⁴, Haiming Wei⁵

Affiliations

¹ Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, China.
² Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. Electronic address: victorzhao@163.com.
³ Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, China. Electronic address: fbq@ustc.edu.cn.
⁵ Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, China. Electronic address: ustcwhm@ustc.edu.cn.

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.

Keywords: GSDME; IL-16; endometriosis; infertility; inflammation; interleukin-16; iron overload; ovarian endometriosis; pyroptosis.

MeSH terms

Animals
Endometriosis* / drug therapy
Female
Humans
Inflammation
Interleukin-16
Mice
Pyroptosis
T-Lymphocytes

Substances

Interleukin-16
Il16 protein, mouse