title: Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  The skin is a potent site for antigen sensitization in the development of experimental allergic rhinitis.
authors.affiliation: Divisions of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Hiroko Saito
authors.initials: HS
authors.lastname: Akei
authors.forename: Eric B
authors.initials: EB
authors.lastname: Brandt
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
authors.forename: Richard T
authors.initials: RT
authors.lastname: Strait
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Manoj R
authors.initials: MR
authors.lastname: Warrier
authors.forename: Gurjit K Khurana
authors.initials: GK
authors.lastname: Hershey
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D006967:Hypersensitivity / Q000209:etiology*; D018793:Interleukin-13 / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009666:Nose / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000502:physiology; D012867:Skin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D018793:Interleukin-13; D020382:Interleukin-18; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse