Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33–basophil axis in mice

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Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder characterized by accumulation of eosinophils in the esophagus. EoE often coexists with atopic dermatitis, a chronic inflammatory skin disease. The impaired skin barrier in patients with atopic dermatitis has been suggested as an entry point for allergic sensitization that triggers development of EoE.


We sought to define the mechanisms whereby epicutaneous sensitization through a disrupted skin barrier induces development of EoE.


To elicit experimental EoE, mice were epicutaneously sensitized with ovalbumin (OVA), followed by intranasal OVA challenge. Levels of esophageal mRNA for TH2 cytokines and the IL-33 receptorIl1rl1 (St2)were measured by using quantitative PCR. Esophageal eosinophil accumulation was assessed by using flow cytometry and hematoxylin and eosin staining.In vivobasophil depletion was achieved with diphtheria toxin treatment ofMcpt8DTRmice, and animals were repopulated with bone marrow basophils. mRNA analysis of esophageal biopsy specimens from patients with EoE was used to validate our findings in human subjects.


Epicutaneous sensitization and intranasal challenge of wild-type mice resulted in accumulation of eosinophils and upregulation of TH2 cytokines andSt2in the esophagus. Disruption of the IL-33–ST2 axis or depletion of basophils reduced these features. Expression of ST2 on basophils was required to accumulate in the esophagus and transfer experimental EoE. Expression ofIL1RL1/ST2mRNA was increased in esophageal biopsy specimens from patients with EoE. Topical OVA application on unstripped skin induced experimental EoE in filaggrin-deficient flaky tail(ft/ft)mice but not in wild-type control orft/ft.St2−/−mice.


Epicutaneous allergic sensitization promotes EoE, and this is critically mediated through the IL-33–ST2–basophil axis.

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