Allergic mechanisms in eosinophilic esophagitis

Abstract

Eosinophilic esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation, and the pathogenic mechanisms have many similarities to other chronic atopic diseases. Studies in animal models and from patients have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which seem to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. In this review our current understandings of the allergic mechanisms that drive eosinophilic esophagitis are outlined, drawing from clinical and translational studies in humans as well as experimental animal models.

Keywords: Allergic mechanism; Antigen sensitization; Atopic; Eosinophilic esophagitis; Pathogenesis; T-helper lymphocyte type 2 immunity.

Fig 1

Proposed allergic mechanisms involved in the pathogenesis of Eosinophilic Esophagitis (EoE). TOP: Proposed mechanism of allergic sensitization in EoE. In the presence of epithelial injury, TSLP production is elicited from epithelium. This primes basophils to produce IL-4 which promotes allergic sensitization after antigen presentation to a naïve T-cell which generates antigen-specific Th2 cells. BOTTOM: Proposed mucosal response in EoE. Subsequet antigen challenge leads to recruitment and expansion of Th2 cells which secrete IL-5 and IL-13, both critical in the recruitment of eosinophils and remodeling of the esophagus. Th2 cells locally promote class-switching of B-cells to produce antigen-specific IgE, which binds to the surface of mast cells. Activation of mast cells leads to the releast of pro-inflammatory mediators such as TGF-β, which promotes remodeling and enhances muscle cell contractility.