Epicutaneous aeroallergen exposure induces systemic T_H2 immunity that predisposes to allergic nasal responses

Background

Atopic individuals are predisposed to mounting vigorous T_H2-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 rhinitis.

Key words: Allergy, atopic, dermatitis, eosinophilia, epicutaneous, lung, nose, sensitization, STAT6

Abbreviations used: AD, Atopic dermatitis, AHR, Airway hyperresponsiveness, Penh, Enhanced pause, STAT6, Signal transducer and activator of transcription 6