Proposed model for the development of allergic inflammation in patients with EoE.
Impaired skin barrier integrity, such as that caused by injury or
FLG mutations, allows for increased allergen penetration
through the epithelium, causing allergic sensitization and release of IL-33 and
TSLP from the epithelium. Secondary to activation by these cytokines, there is
increased trafficking of basophils through the bloodstream to the esophagus.
Later, direct exposure of allergens to the esophageal epithelium leads to the
release of TSLP and IL-33, which induce IL-4 production from basophils and
subsequent release of IL-5 and IL-13 from TH2 cells. IL-13 causes
esophageal epithelial barrier impairment and increased allergen exposure by
decreasing desmoglein 1 (DSG1) and increasing calpain 14
(CAPN14) expression. Additionally, IL-13 induces CCL26
production from the epithelium, which, in combination with IL-5, causes
eosinophil infiltration into the esophagus.