The Immunologic Mechanisms of Eosinophilic Esophagitis

Abstract

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that is triggered by food and/or environmental allergens and is characterized by a clinical and pathologic phenotype of progressive esophageal dysfunction due to tissue inflammation and fibrosis. EoE is suspected in patients with painful swallowing, among other symptoms, and is diagnosed by the presence of 15 or more eosinophils per high-power field in one or more of at least four esophageal biopsy specimens. The prevalence of EoE is increasing and has now reached rates similar to those of other chronic gastrointestinal disorders such as Crohn's disease. In recent years, our understanding of the immunologic mechanisms underlying this condition has grown considerably. Thanks to new genetic, molecular, cellular, animal, and translational studies, we can now postulate a detailed pathway by which exposure to allergens results in a complex and coordinated type 2 inflammatory cascade that, if not intervened upon, can result in pain on swallowing, esophageal strictures, and food impaction. Here, we review the most recent research in this field to synthesize and summarize our current understanding of this complex and important disease.

Keywords: Eosinophilic esophagitis; Food allergy; Immunology; Inflammation.

Fig. 1

The inflammatory cycle of EoE

Fig. 2

The inflammatory mechanisms of EoE. Allergen interaction with antigen-presenting cells (APC) leads to innate and adaptive lymphocyte responses and characteristic type 2 cytokine production. Signaling in the esophageal epithelial cells broadens the inflammatory response through production of effector and chemoattractant molecules which mediate recruitment and activation of eosinophils (EO), mast cells (MC), and basophils (BASO). Downregulation of cell adhesion molecules contributes to impaired mucosal integrity. Ultimately, persistent inflammation results in the development of esophageal fibrosis