The pathogenesis of chronic eosinophilic esophagitis in SHARPIN-deficient mice

Experimental and Molecular Pathology
Syu-Jhe ChienJohn P Sundberg

Abstract

Increased numbers of eosinophils in the esophagus are common in several esophageal and systemic diseases, and a prominent feature of eosinophilic esophagitis. Mouse models can provide insight into the mechanisms of eosinophil infiltration and their pathogenic role. SHARPIN-deficient cpdm mice develop a chronic proliferative dermatitis and an esophagitis characterized by epithelial hyperplasia and the accumulation of eosinophils in the serosa, submucosa, lamina propria and epithelium of the esophagus. We conducted a detailed investigation of the pathogenesis of the esophagitis by light microscopy, immunohistochemistry, and gene expression as the mice aged from 4 to 10 weeks. The thickness of the esophageal epithelium and the number of eosinophils in the esophagus both increased with age. There were scattered apoptotic epithelial cells in mice at 6-10 weeks of age that reacted with antibodies to activated caspase 3 and caspase 9. The expression of CCL11 (eotaxin-1), IL4, IL13 and TSLP was increased in cpdm mice compared with wild type (WT) mice, and there was no change in the expression of CCL24 (eotaxin-2), IL5 and IL33. The expression of chitinase-like 3 and 4 (YM1 and YM2) proteins, markers of type 2 inflammation, was greatly ...Continue Reading

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Citations

Jan 28, 2020·Journal of Leukocyte Biology·Joshua D WebsterDomagoj Vucic
Apr 21, 2017·Journal of Internal Medicine·C BlanchardH-U Simon
Mar 21, 2019·Biomedical Optics Express·Dawei LiXingde Li
Jul 17, 2020·Frontiers in Cell and Developmental Biology·Joshua D Webster, Domagoj Vucic
Feb 4, 2021·Digestive Diseases and Sciences·Amanda H LimNam Q Nguyen

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