dc.contributor.author | Østvik, Ann Elisabet | |
dc.contributor.author | Svendsen, Tarjei Dahl | |
dc.contributor.author | Granlund, Atle van Beelen | |
dc.contributor.author | Doseth, Berit | |
dc.contributor.author | Skovdahl, Helene Kolstad | |
dc.contributor.author | Bakke, Ingunn | |
dc.contributor.author | Thorsvik, Silje | |
dc.contributor.author | Afroz, Wahida | |
dc.contributor.author | Walaas, Gunnar Andreas | |
dc.contributor.author | Mollnes, Tom Eirik | |
dc.contributor.author | Gustafsson, Björn | |
dc.contributor.author | Sandvik, Arne Kristian | |
dc.contributor.author | Bruland, Torunn | |
dc.date.accessioned | 2021-01-08T12:01:40Z | |
dc.date.available | 2021-01-08T12:01:40Z | |
dc.date.issued | 2020-02-05 | |
dc.description.abstract | <i>Background and Aims</i> - Intestinal epithelial cells [IECs] secrete cytokines that recruit immune cells to the mucosa and regulate immune responses that drive inflammation in inflammatory bowel disease [IBD]. However, experiments in patient-derived IEC models are still scarce. Here, we aimed to investigate how innate immunity and IEC-specific pattern recognition receptor [PRR] signalling can be involved in an enhanced type I interferon [IFN] gene signature observed in colon epithelium of patients with active IBD, with a special focus on secreted ubiquitin-like protein ISG15.<p>
<p><i>Methods</i> - Gene and protein expression in whole mucosa biopsies and in microdissected human colonic epithelial lining, in HT29 human intestinal epithelial cells and primary 3D colonoids treated with PRR-ligands and cytokines, were detected by transcriptomics, <i>in situ</i> hybridisation, immunohistochemistry, western blots, and enzyme-linked immunosorbent assay [ELISA]. Effects of IEC-secreted cytokines were examined in human peripheral blood mononuclear cells [PBMCs] by multiplex chemokine profiling and ELISA.<p>
<p><i>Results</i> - The type I IFN gene signature in human mucosal biopsies was mimicked in Toll-like receptor TLR3 and to some extent tumour necrosis factor [TNF]-treated human IECs. In intestinal biopsies, ISG15 expression correlated with expression of the newly identified receptor for extracellular ISG15, LFA-1 integrin. ISG15 was expressed and secreted from HT29 cells and primary 3D colonoids through both JAK1-pSTAT-IRF9-dependent and independent pathways. In experiments using PBMCs, we show that ISG15 releases IBD-relevant proinflammatory cytokines such as CXCL1, CXCL5, CXCL8, CCL20, IL1, IL6, TNF, and IFNγ.<p>
<p><i>Conclusions</i> - ISG15 is secreted from primary IECs upon extracellular stimulation, and mucosal ISG15 emerges as an intriguing candidate for immunotherapy in IBD. | en_US |
dc.identifier.citation | Østvik, Svendsen, Granlund, Doseth, Skovdahl, Bakke, Thorsvik, Afroz, Walaas, Mollnes, Gustafsson, Sandvik, Bruland. Intestinal epithelial cells express immunomodulatory ISG15 during active ulcerative colitis and Crohn's disease. Journal of Crohn's and colitis. 2020;14(7):920-934 | en_US |
dc.identifier.cristinID | FRIDAID 1814597 | |
dc.identifier.doi | 10.1093/ecco-jcc/jjaa022 | |
dc.identifier.issn | 1873-9946 | |
dc.identifier.issn | 1876-4479 | |
dc.identifier.uri | https://hdl.handle.net/10037/20231 | |
dc.language.iso | eng | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.journal | Journal of Crohn's and colitis | |
dc.relation.projectID | info:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/ | en_US |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2020 The Author(s) | en_US |
dc.subject | VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710 | en_US |
dc.subject | VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710 | en_US |
dc.title | Intestinal epithelial cells express immunomodulatory ISG15 during active ulcerative colitis and Crohn's disease | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |