Article Dans Une Revue Cell Année : 2024

Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair

Résumé

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.

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Recherche Data Gouv

Cite 10.57745/MB71AU Jeu de données JENA, Kautilya K; MAMBU, Julien; BOEHMER, Daniel; SPOSITO, Benedetta; MILLET, Virginie; DE SOUSA CASAL, Joshua; MUENDLEIN, Hayley; SPREAFICO, Roberto; FENOUIL, Romain; SPINELLI, Lionel; WURBEL, Sarah; RIQUIER, Chloé; GALLAND, Franck; NAQUET, Philippe; CHASSON, Lionel; ELKINS, Megan; MITSIALIS, Vanessa; KETELUT-CARNEIRO, Natalia; BUGDA GWILT, Katlynn; THIAGARAJAH, Jay; RUAN, Hai-Bin; LIN, Zhaoyu; LIEN, Egil; SHAO, Feng; CHOU, Janet; POLTORAK, Alexander; ORDOVAS-MONTANES, Jose; FITZGERALD, Kate; SNAPPER, Scott; BROGGI, Achille; ZANONI, Ivan, 2025, "ABlab_IFNLGutRestitution_IonTorrent_bulkRNA-seq", https://doi.org/10.57745/MB71AU, Recherche Data Gouv, V1

Dates et versions

hal-04767889 , version 1 (05-11-2024)

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Kautilya K Jena, Julien Mambu, Daniel Boehmer, Benedetta Sposito, Virginie Millet, et al.. Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair. Cell, In press, Online ahead of print. ⟨10.1016/j.cell.2024.10.010⟩. ⟨hal-04767889⟩
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