细胞焦亡诱导的 T 细胞来源的活性白介素-16 在卵巢子宫内膜异位症的发展中具有驱动作用。
Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.
机构信息
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.
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.
出版信息
Cell Rep Med. 2024 Mar 19;5(3):101476. doi: 10.1016/j.xcrm.2024.101476.
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.
子宫内膜异位症影响了 6%-10%的女性，常导致疼痛和不孕，但其潜在的炎症机制尚未被充分理解。我们在野生型和 IL16KO 小鼠中建立了子宫内膜异位症模型，揭示了 IL-16 在引发与子宫内膜异位症相关的炎症中的驱动作用。通过体外系统，我们证实了铁过载诱导的 GSDME 介导的细胞焦亡是 IL-16 激活和释放的关键触发因素。此外，我们的研究导致了 Z30702029 的开发，这是一种抑制 GSDME-NTD 介导的细胞焦亡的化合物，有望成为子宫内膜异位症的治疗干预手段。重要的是，我们的发现超出了子宫内膜异位症的范围，强调了 GSDME 介导的细胞焦亡是 IL-16 释放的更广泛途径，并为各种炎症性疾病的潜在治疗方法提供了新的思路。
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