ArticleJournal of Crohn's & colitis2020
Intestinal Epithelial Cells Express Immunomodulatory ISG15 During Active Ulcerative Colitis and Crohn's Disease.
Article in Journal of Crohn's & colitis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Mucosal p-STAT1/3 correlates with histologic disease activity in Crohn's disease and is responsive to filgotinib.Tissue barriers · 2023Trial
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- Article
- Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis.iScience · 2026Article
- Glycocholic acid inhibits TRIB3-ID1 axis to acelerate colitis progression via suppressing intestinal stem cell renewal.Nature communications · 2026Article
- Patient-matched transcriptomics of in vivo and in vitro colonic epithelium substantiate organoids as a translational model for ulcerative colitis.Scientific reports · 2026Article
- Type I and III interferons synergize with TNF to promote virally-triggered damage to the intestinal epithelium.bioRxiv : the preprint server for biology · 2026Article
- Type I interferon signaling promotes mucosal inflammation in murine models of colitis.bioRxiv : the preprint server for biology · 2026Article
- mCellular and molecular life sciences : CMLS · 2025Article
- U1 RNA Detected by Toll-Like Receptor 3 Plays a Role in the Pathogenesis of Pterygium.Investigative ophthalmology & visual science · 2025Article
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- ISG15 modulates inflammatory profiles and ability to activate CD8 + T cells in bone marrow-derived dendritic cells.Cellular and molecular life sciences : CMLS · 2025Article
- Secreted ISG15 induced by Chlamydia trachomatis infection exerts immunomodulatory effects on IFN-γ defense and inflammation.PLoS pathogens · 2025Article
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- An AI-assisted morphoproteomic approach is a supportive tool in esophagitis-related precision medicine.EMBO molecular medicine · 2025Article
- Tofacitinib and budesonide treatment affect stemness and chemokine release in IBD patient-derived colonoids.Scientific reports · 2025Article
- The SERPINB4 gene mutation identified in twin patients with Crohn's disease impaires the intestinal epithelial cell functions.Scientific reports · 2025Article
- The Cell-Specific Effects of JAK1 Inhibitors in Ulcerative Colitis.Journal of clinical medicine · 2025Review
- The intestinal interferon system and specialized enterocytes as putative drivers of HIV latency.Frontiers in immunology · 2025Review
- cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsIntestinal 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.
methodsGene 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, in situ 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.
resultsThe 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.
conclusionsISG15 is secreted from primary IECs upon extracellular stimulation, and mucosal ISG15 emerges as an intriguing candidate for immunotherapy in IBD.
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