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http://purl.uniprot.org/citations/37884352http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37884352http://www.w3.org/2000/01/rdf-schema#comment"

Objective

We sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis.

Design

Experimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation. We further used RNA-sequencing (RNA-Seq), RNAScope and Gene Ontology analysis, western blot analysis and co-immunoprecipitation, confocal microscopy and intestinal epithelial cell (IEC)-derived three-dimensional organoids to investigate the underlying molecular mechanisms. Results were validated using samples from patients with IBD and non-IBD control subjects by a combination of RNA-Seq, organoids and immunostainings.

Results

In IBD, IL20 levels were induced during remission and were significantly higher in antitumour necrosis factor responders versus non-responders. IL-20RA and IL-20RB were present on IECs from patients with IBD and IL-20-induced STAT3 and suppressed interferon (IFN)-STAT2 signalling in these cells. In IBD, experimental dextran sulfate sodium (DSS)-induced colitis and mucosal healing, IECs were the main producers of IL-20. Compared with wildtype controls, Il20-/-, Il20ra-/- and Il20rb-/- mice were more susceptible to experimental DSS-induced colitis. IL-20 deficiency was associated with increased IFN/STAT2 activity in mice and IFN/STAT2-induced necroptotic cell death in IEC-derived organoids could be markedly blocked by IL-20. Moreover, newly generated Stat2ΔIEC mice, lacking STAT2 in IECs, were less susceptible to experimental colitis compared with wildtype controls and the administration of IL-20 suppressed colitis activity in wildtype animals.

Conclusion

IL-20 controls colitis and mucosal healing by interfering with the IFN/STAT2 death signalling pathway in IECs. These results indicate new directions for suppressing gut inflammation by modulating IL-20-controlled STAT2 signals."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.org/dc/terms/identifier"doi:10.1136/gutjnl-2023-329628"xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Becker C."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Hartmann A."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Rath T."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Trajanoski Z."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Gunther C."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Neurath M.F."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Wirtz S."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Siegmund B."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Atreya R."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Danese S."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Finotto S."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Vetrano S."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Sturm G."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Kuhl A.A."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Dressel A."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Siebler J."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Chiriac M.T."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Hundorfean G."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Hracsko Z."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Wittner L."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Zundler S."xsd:string
http://purl.uniprot.org/citations/37884352http://purl.uniprot.org/core/author"Gamez-Belmonte R."xsd:string
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