Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses

Background: Atopic individuals are predisposed to mounting vigorous T(H)2-type immune responses to environmental allergens. The skin is often the first organ that manifests allergic disease and may provide an early entry point for antigen sensitization. Objective: We sought to determine whether epicutaneous exposure to the aeroallergen Aspergillus fumigatus induces nasal allergic responses. Furthermore, we aimed to examine the mechanism involved. Methods: Wild-type and signal transducer and activator of transcription 6 (STAT6)-deficient mice were exposed to epicutaneous A fumigatus and control antigen ovalbumin. Nasal inflammation and responsiveness to methacholine were monitored. Results: Exposure to epicutaneous A fumigatus antigen induced a marked atopic dermatitis-like phenotype in a manner significantly more efficient than epicutaneous ovalbumin. A single A fumigatus intranasal challenge induced clinical nasal responses and hyperresponsiveness to methacholine in the nose as manifested by nasal symptoms, accompanied by allergic airway and nasal inflammation. Mechanistic analysis using gene-targeted mice revealed that the clinical nasal responses and hyperresponsiveness were STAT6-dependent. Although STAT6 was required for changes in nasal responses, it was not required for epicutaneous pathology except eosinophilia. Conclusion: Epicutaneous exposure to the aeroallergen A fumigatus potently primes for STAT6-dependent nasal responses. These results draw attention to the cooperative interaction between the nasal tract and skin. Clinical implications: The skin is a potent site for antigen sensitization in the development of experimental allergic.