Cell · 2024
Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jena Kautilya K, Mambu Julien, Boehmer Daniel, Sposito Benedetta, Millet Virginie, de Sousa Casal Joshua, Muendlein Hayley I, Spreafico Roberto, Fenouil Romain, Spinelli Lionel, Wurbel Sarah, Riquier Chloé, Galland Franck, Naquet Philippe, Chasson Lionel, Elkins Megan, Mitsialis Vanessa, Ketelut-Carneiro Natália, Bugda Gwilt Katlynn, Thiagarajah Jay R, Ruan Hai-Bin, Lin Zhaoyu, Lien Egil, Shao Feng, Chou Janet, Poltorak Alexander, Ordovas-Montanes Jose, Fitzgerald Katherine A, Snapper Scott B, Broggi Achille, Zanoni Ivan
Аннотация
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.