Involvement of interleukin-18 in the pathogenesis of human eosinophilic esophagitis

•IL-18 is elevated in a number of eosinophilic allergic diseases including EoE.•IL-18 stimulates iNKT cells without T cell receptor (TCR) engagement.•Study provides a rationale for CD1d-restricted iNKT cells activation in human EoE.•Importantly, IL-18 may be a diagnostic and therapeutic target molecule for human EoE.

IL-18 is induced in food allergy and EoE is food allergen-induced disease. Therefore, we tested the hypothesis whether IL-18 is involved in food allergen-induced EoE pathogenesis. Accordingly, we examined normal SPT + and SPT − EoE patient blood and biopsy samples for IL-18, IL-18Rα, ICAM and VCAM expression. Herein, we show increased IL-18 level is highly significant in food allergen SPT + compared to SPT − EoE patients. We also report that IL-18Rα + cells and mRNA levels are induced in the esophageal biopsies of EoE patients and blood IL-18 levels correlate with esophageal eosinophilia (P < 0.01). Additionally, we report that the levels of esophageal eosinophil and mast cells correlate with ICAM expression in human EoE. Mechanistically, we show that IL-18 in vitro stimulates iNKT cells and endothelial cells and induce eosinophil active cytokines IL-5 and IL-13. We provide the evidence that IL-18 is critical cytokine involved in activation of iNKT cells and ICAM in promoting human EoE.