ArticleInflammatory bowel diseases2015
Eosinophils and IL-33 Perpetuate Chronic Inflammation and Fibrosis in a Pediatric Population with Stricturing Crohn's Ileitis.
Article in Inflammatory bowel diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Histopathology Scoring Systems of Stenosis Associated With Small Bowel Crohn's Disease: A Systematic Review.Gastroenterology · 2020Pooled it
- Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential.Nature reviews. Immunology · 2026Review
- Crohn's lymphoid aggregates with endothelial clusters colocalise with submucosal fibrosis in fibrostenosing Crohn's disease.The Journal of pathology · 2026Article
- Emerging Insights into the Inflammatory Phenotypes of Eosinophilic Esophagitis.Journal of inflammation research · 2026Review
- The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn's disease-like ileitis.Journal of Crohn's & colitis · 2025Article
- Review
- Effect of Tissue Eosinophilia on the Disease Outcome of Pediatric With Inflammatory Bowel Disease (IBD).JGH open : an open access journal of gastroenterology and hepatology · 2025Article
- Review
- Spatial adaptation of eosinophils and their emerging roles in homeostasis, infection and disease.Nature reviews. Immunology · 2024Review
- Eosinophils mitigate intestinal fibrosis while promoting inflammation in a chronic DSS colitis model and co-culture model with fibroblasts.Scientific reports · 2024Article
- Conserved and tissue-specific immune responses to biologic scaffold implantation.Acta biomaterialia · 2024Article
- Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.Journal of clinical medicine · 2024Review
- Mechanisms and therapeutic research progress in intestinal fibrosis.Frontiers in medicine · 2024Article
- Conserved and tissue-specific immune responses to biologic scaffold implantation.bioRxiv : the preprint server for biology · 2023Article
- Parallel origins and functions of T cells and ILCs.Clinical and experimental immunology · 2023Review
- Cellular and Molecular Mechanisms of Intestinal Fibrosis.Gut and liver · 2023Review
- Molecular Basis of Intestinal Fibrosis in Inflammatory Bowel Disease.Inflammatory intestinal diseases · 2023Review
- Full-length IL-33 augments pulmonary fibrosis in an ST2- and Th2-independent, non-transcriptomic fashion.Cellular immunology · 2023Article
- Review
- Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases.Physiological reviews · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFibrostenosis and stricture are well-recognized endpoints in Crohn's disease (CD). We hypothesized that stricturing CD is characterized by eosinophilia and epithelial IL-33. We proposed that eosinophil exposure to IL-33 would perpetuate inflammatory chronicity and subsequent fibrostenosis.
methodsWe performed a retrospective study of 74 children with inflammatory and stricturing ileal CD comparing clinicopathological features to immunohistochemical measures of eosinophilia and IL-33. To scrutinize eosinophil patterns, we developed a novel eosinophil peroxidase score encompassing number, distribution, and degranulation. Human eosinophils and intestinal fibroblasts were cultured with IL-33 and IL-13, and inflammatory and remodeling parameters were assessed. Antieosinophil therapy was also administered to the Crohn's-like ileitis model (SAMP1/SkuSlc).
resultsOur novel eosinophil peroxidase score was more sensitive than H&E staining, revealing significant differences in eosinophil patterns, comparing inflammatory and stricturing pediatric CD. A significant relationship between ileal eosinophilia and complicated clinical/histopathological phenotype including fibrosis was determined. IL-33 induced significant eosinophil peroxidase secretion and IL-13 production. Exposure to eosinophils in the presence of IL-33, "primed" fibroblasts to increase proinflammatory cytokines (TNF-α, IL-1β, and IL-6), eosinophil-associated chemokines (CCL24 and CCL26), and IL-13Rα2 production. Production of fibrogenic molecules (collagen 1A2, fibronectin, and periostin) increased after exposure of "primed" fibroblasts to IL-13. Epithelial-IL-33 was increased in pediatric Crohn's ileitis and strongly associated with clinical and histopathological activity, ileal eosinophilia, and complicated fibrostenotic disease. SAMP1/SkuSlc eosinophil-targeted treatment resulted in significant improvements in inflammation and remodeling.
conclusionsOur study of specimens from pediatric patients with ileal CD linked eosinophil patterns and IL-33 to fibrosis and suggested that these may contribute to the perpetuation of inflammation and subsequent stricture in pediatric CD.
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