The Evolving Role of Eosinophils in Eosinophilic Esophagitis: Mechanisms, Crosstalk, and Therapeutic Perspectives

Introduction: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease characterized by eosinophilic infiltration, epithelial barrier dysfunction, and progressive tissue remodeling. Increasing evidence identifies eosinophils as central drivers of inflammation and fibrosis, linking EoE to type 2 immune responses and allergic disorders. However, the molecular mechanisms underlying eosinophil-mediated esophageal damage and their interaction with gastroesophageal reflux disease (GERD) remain incompletely understood. Material and Methods: A comprehensive narrative review of the current literature was conducted, focusing on studies investigating eosinophil biology, inflammatory signaling pathways, epithelial remodeling, fibrosis, and therapeutic targets in EoE. Clinical, translational, and experimental studies evaluating the association between EoE, GERD, and allergic comorbidities were critically analyzed. Results: Available evidence demonstrates that eosinophils actively contribute to EoE pathogenesis through the release of cytotoxic granule proteins, cytokines, chemokines, and lipid mediators, leading to chronic inflammation and fibrostenotic remodeling. Dysregulation of type 2 cytokines, particularly IL-4, IL-5, and IL-13, plays a pivotal role in disease progression and immune cell recruitment. Significant overlap between EoE and GERD suggests shared inflammatory mechanisms and diagnostic challenges. Furthermore, EoE frequently coexists with systemic allergic diseases, supporting the concept of a broader atopic inflammatory phenotype. Emerging biologic therapies targeting eosinophilic and type 2 inflammatory pathways have shown promising efficacy in reducing symptoms and histologic activity. Conclusions: Eosinophils represent key regulators of EoE pathobiology and constitute promising biomarkers and therapeutic targets. A deeper understanding of eosinophil-driven inflammatory networks may improve diagnostic accuracy, patient stratification, and the development of personalized therapeutic strategies for EoE and related esophageal inflammatory disorders.