Thymic stromal lymphopoietin as a therapeutic target for the treatment of eosinophilic esophagitis

Vollständiger Abstract

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Thymic stromal lymphopoietin (TSLP) is a key upstream epithelial cytokine and its over-expression is associated with inflammation leading to immune dysfunction, epithelial barrier disruption, and tissue remodeling. TSLP is implicated in the pathogenesis of multiple atopic diseases including asthma, chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis (EoE). EoE is a chronic, type 2 (T2) inflammatory disease linked to a delayed-type hypersensitivity response to food antigens and characterized by eosinophil-predominant mucosal inflammation and esophageal dysfunction. TSLP expression and TSLP-mediated T2 inflammatory activity is elevated in esophageal biopsies in patients with active EoE compared with patients with inactive EoE and healthy individuals. In phase 3 clinical trials, a monoclonal antibody against TSLP, tezepelumab, has shown significant improvements in clinical outcomes compared with placebo in other atopic conditions that have a shared T2 inflammatory disease pathology and epithelial remodeling pathway with EoE such as asthma and chronic rhinosinusitis with nasal polyps. In this review, we present evidence of TSLP involvement in mediating and exacerbating EoE pathology and discuss how targeting TSLP activity could be a viable therapeutic option for EoE treatment.