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Herein, we report an ex vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant proinflammatory (IL-13) or profibrotic (TGF-\u03b2) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-\u03b2 increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13\u2013treated cocultures demonstrated increased secretion of GRO-\u03b1, IL-8, and macrophage colony-stimulating factor and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-\u03b2\u2013treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13\u2013treated coculture conditions. When eosinophils from TGF-\u03b2\u2013treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with granulocyte macrophage colony-stimulating factor alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsy specimens. Our results demonstrate that disease-relevant proinflammatory and profibrotic signals present in the esophagus of patients with eosinophilic esophagitis cause distinct profiles of eosinophil activation and gene expression.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae102","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T12:09:29Z","timestamp":1715256569000},"page":"1007-1020","source":"Crossref","is-referenced-by-count":11,"title":["Eosinophil specialization is regulated by exposure to the esophageal epithelial microenvironment"],"prefix":"10.1093","volume":"116","author":[{"given":"Julia L M","family":"Dunn","sequence":"first","affiliation":[{"name":"Division of Allergy & Immunology, Cincinnati Children's Hospital Medical Center , 3333 Burnet Avenue, Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Szep","sequence":"additional","affiliation":[{"name":"Division of Allergy & 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