美国哈佛医学院Ivan Zanoni等研究人员合作发现，III型干扰素诱导肠道上皮细胞的焦亡并损害黏膜修复。相关论文于2024年11月4日在线发表在《细胞》杂志上。
研究人员探讨了干扰素如何影响肠道黏膜损伤后的修复过程。研究人员发现，III型干扰素，而非I型或II型干扰素，通过诱导Z-DNA结合蛋白1（ZBP1）上调来延迟上皮细胞的再生。肠道损伤后形成的Z-核酸被ZBP1感知，导致半胱天冬酶-8激活并切割gasderminC（GSDMC）。
切割的GSDMC通过焦亡驱动上皮细胞死亡，并分别延迟结肠炎或辐射后大肠或小肠的修复。III型干扰素/ZBP1/半胱天冬酶-8/GSDMC轴在炎症性肠病（IBD）患者中也处于活跃状态。这些研究结果突出了III型干扰素延迟肠道修复的能力，这对于IBD患者或接受放射治疗的个体具有重要意义。
据了解，组织损伤和修复是炎症的标志。尽管关于调控组织损伤的机制已有大量信息，但关于炎症如何影响修复的机制性见解仍然缺乏。
附：英文原文
Title: Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair
Author: Kautilya K. Jena, Julien Mambu, Daniel Boehmer, Benedetta Sposito, Virginie Millet, Joshua de Sousa Casal, Hayley I. Muendlein, Roberto Spreafico, Romain Fenouil, Lionel Spinelli, Sarah Wurbel, Chloé Riquier, Franck Galland, Philippe Naquet, Lionel Chasson, Megan Elkins, Vanessa Mitsialis, Natália Ketelut-Carneiro, Katlynn Bugda Gwilt, Jay R. Thiagarajah, Hai-Bin Ruan, Zhaoyu Lin, Egil Lien, Feng Shao, Janet Chou, Alexander Poltorak, Jose Ordovas-Montanes, Katherine A. Fitzgerald, Scott B. Snapper, Achille Broggi, Ivan Zanoni
Issue&Volume: 2024-11-04
Abstract: Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight into how inflammation affects repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa. We found that type III, not type I or type II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed following intestinal damage are sensed by ZBP1, leading to caspase-8 activation and the cleavage of gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays repair of the large or small intestine after colitis or irradiation, respectively. The type III interferon/ZBP1/caspase-8/GSDMC axis is also active in patients with inflammatory bowel disease (IBD). Our findings highlight the capacity of type III interferons to delay gut repair, which has implications for IBD patients or individuals exposed to radiation therapies.
DOI: 10.1016/j.cell.2024.10.010
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01158-9