ArticlePloS one2016
JAK-STAT6 Pathway Inhibitors Block Eotaxin-3 Secretion by Epithelial Cells and Fibroblasts from Esophageal Eosinophilia Patients: Promising Agents to Improve Inflammation and Prevent Fibrosis in EoE.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 79 citations in OpenAlex.
- Beyond the Surface: Exploring Altered Esophageal Distensibility and Compliance in Eosinophilic Esophagitis.Digestive diseases and sciences · 2026Review
- Eosinophilic gastrointestinal diseases.Nature reviews. Disease primers · 2026Review
- Review
- Advances in Management of Eosinophilic Esophagitis in Pediatrics.Paediatric drugs · 2026Review
- Effects of proton pump inhibitors on remodeling and fibrosis in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2026Article
- Eosinophilic Esophagitis: Mechanisms of Disease and Approach to Treatment.Current allergy and asthma reports · 2026Review
- Balancing therapeutic benefits and hidden risks of proton pump inhibitors in pediatric practice: a narrative review and update.Clinical and experimental pediatrics · 2026Article
- The Immune Architecture of Eosinophilic Esophagitis: Mechanisms, Therapeutic Targets, and Precision Management.ImmunoTargets and therapy · 2026Review
- Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Overlapping type 2, barrier, and remodeling endotypes shape clinical expression in eosinophilic esophagitis.Frontiers in immunology · 2026Review
- Emerging Insights into the Inflammatory Phenotypes of Eosinophilic Esophagitis.Journal of inflammation research · 2026Review
- Mouse models of eosinophilic esophagitis: molecular and translational insights.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- The efficacy of JAK inhibitors in adult eosinophilic colitis with atopic dermatitis; four cases report.Clinical journal of gastroenterology · 2025Article
- Effect of benralizumab on histopathology and inflammatory signatures in a clinical cohort of eosinophilic esophagitis.Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus · 2025Article
- Inhalation and inflammation: examining aeroallergens and eosinophilic esophagitis.Frontiers in allergy · 2025Review
- Article
- Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.Journal of clinical medicine · 2024Review
- Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024Review
- Assessment of the Severity and the Remission Criteria in Eosinophilic Esophagitis.Biomedicines · 2023Review
- IL-13-induced STAT3-dependent signaling networks regulate esophageal epithelial proliferation in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlthough most studies on treatments for eosinophilic esophagitis (EoE) have focused on effects in the epithelium, EoE is a transmural disease. Eosinophils that infiltrate the subepithelial layers of the esophagus lead to fibrosis and the serious complications of EoE, and current therapies have shown minimal effects on this fibrosis. We aimed to elucidate T helper (Th)2 cytokine effects on esophageal fibroblasts and to explore potential fibroblast-targeted therapies for EoE.
methodsWe established telomerase-immortalized fibroblasts from human esophageal biopsies. We stimulated these esophageal fibroblasts with Th2 cytokines, and examined effects of omeprazole and inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT6) pathway (AS1517499, leflunomide, and ruxolitinib) on STAT6 phosphorylation, STAT6 nuclear translocation, and eotaxin-3 expression. We also measured the effects of these inhibitors in esophageal epithelial cells stimulated with Th2 cytokines.
resultsAs in esophageal epithelial cells, Th2 cytokines increased STAT6 phosphorylation, STAT6 nuclear translocation, eotaxin-3 transcription and protein secretion in esophageal fibroblasts. Unlike in epithelial cells, however, omeprazole did not inhibit cytokine-stimulated eotaxin-3 expression in fibroblasts. In contrast, JAK-STAT6 pathway inhibitors decreased cytokine-stimulated eotaxin-3 expression in both fibroblasts and epithelial cells.
conclusionsOmeprazole does not inhibit Th2 cytokine-stimulated eotaxin-3 expression by esophageal fibroblasts, suggesting that PPIs will have limited impact on subepithelial EoE processes such as fibrosis. JAK-STAT6 pathway inhibitors block Th2 cytokine-stimulated eotaxin-3 expression both in fibroblasts and in epithelial cells, suggesting a potential role for JAK-STAT inhibitors in treating both epithelial inflammation and subepithelial fibrosis in EoE.
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