Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

• Published in: Frontiers in physiology Vol. 12; p. 815842
• Main Authors: Racca, Francesca, Pellegatta, Gaia, Cataldo, Giuseppe, Vespa, Edoardo, Carlani, Elisa, Pelaia, Corrado, Paoletti, Giovanni, Messina, Maria Rita, Nappi, Emanuele, Canonica, Giorgio Walter, Repici, Alessandro, Heffler, Enrico
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12.01.2022
• Subjects: eosinophilic esophagitis; pathophysiology; Physiology; precision medicine; therapeutic targets; type 2 inflammation; precision medicine; therapeutic targets; type 2 inflammation; eosinophilic esophagitis; pathophysiology
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2021.815842

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.