Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice.
OBJECTIVE
Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE.


METHODS
Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined.


RESULTS
We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent.


CONCLUSIONS
These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.
Akei
Hiroko Saito
HS
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Mishra
Anil
A
Blanchard
Carine
C
Rothenberg
Marc E
ME
D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils; D004941:Esophagitis / Q000276:immunology*; D005818:Genetic Engineering; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin