Eosinophils and IL-33 Perpetuate Chronic Inflammation and Fibrosis in a Pediatric Population with Stricturing Crohn's Ileitis.

摘要: Background Fibrostenosis and stricture are well-recognized endpoints in Crohn's disease (CD). We hypothesized that stricturing CD is characterized by eosinophilia epithelial IL-33. proposed eosinophil exposure to IL-33 would perpetuate inflammatory chronicity subsequent fibrostenosis. Methods performed a retrospective study of 74 children with ileal comparing clinicopathological features immunohistochemical measures To scrutinize patterns, we developed novel peroxidase score encompassing number, distribution, degranulation. Human eosinophils intestinal fibroblasts were cultured IL-13, remodeling parameters assessed. Antieosinophil therapy was also administered the Crohn's-like ileitis model (SAMP1/SkuSlc). Results Our more sensitive than H&E staining, revealing significant differences pediatric CD. A relationship between complicated clinical/histopathological phenotype including fibrosis determined. induced secretion IL-13 production. Exposure presence IL-33, "primed" increase proinflammatory cytokines (TNF-α, IL-1β, IL-6), eosinophil-associated chemokines (CCL24 CCL26), IL-13Rα2 Production fibrogenic molecules (collagen 1A2, fibronectin, periostin) increased after IL-13. Epithelial-IL-33 strongly associated clinical histopathological activity, eosinophilia, fibrostenotic disease. SAMP1/SkuSlc eosinophil-targeted treatment resulted improvements inflammation remodeling. Conclusions specimens from patients linked patterns suggested these may contribute perpetuation