Advancing the understanding of eosinophilic esophagitis: From pathogenesis to novel therapies

Figure 1 Pathogenesis of eosinophilic esophagitis with current and investigational therapeutic targets. The horizontal cascade depicts antigen exposure, epithelial barrier dysfunction with alarmin release [thymic stromal lymphopoietin, interleukin (IL)-33, IL-25], Th2/type 2 innate lymphoid cells immune activation with IL-4, IL-5, and IL-13 production, eosinophil recruitment and activation, and tissue remodeling/fibrostenosis. The therapeutic class intervening at each step is shown below the corresponding cascade step, including dietary elimination, anti-alarmin biologics (tezepelumab), Th2 cytokine-targeted biologics (dupilumab, cendakimab, mepolizumab, reslizumab, benralizumab, lirentelimab), topical corticosteroids and proton-pump inhibitors, and endoscopic dilation. DSG-1: Desmoglein-1; CAPN14: Calpain 14; TSLP: Thymic stromal lymphopoietin; IL: Interleukin; ILC2: Type 2 innate lymphoid cells; CCL26: Chemokine (C-C motif) ligand 26; eos: Eosinophil; HPF: High-power field; FED: Food elimination diet; FDA: Food and Drug Administration.