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Type III interferons induce pyroptosis in gut epithelial cells and impair tissue repair upon intestinal injury.

GSE277150 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/11/01 Platform GPL24247
Summary
Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on 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 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 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 important implications for IBD patients or individuals exposed to radiation therapies.
Published in
Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair
Jena KK, Mambu J, Boehmer D et al. · Cell 2024 · PMID 39500322 · doi:10.1016/j.cell.2024.10.010
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Also filed as BioProject PRJNA1160875 and SRA study SRP532559. Searching any of these in the dataset finder brings you back here.

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