title: Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.
abstract: BACKGROUND
  Oral exposure to food allergens may be limited in infancy, and the initial site of antigen exposure likely plays an important role in food allergy induction.
  
  
  OBJECTIVE
  To examine the impact of different routes of exposure by using milk allergens, with and without adjuvant, on sensitization.
  
  
  METHODS
  C3H/HeJ mice were repeatedly exposed to the milk allergen α-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneous, intranasal, and sublingual. Anaphylaxis severity was assessed by symptoms and body temperature in response to oral challenge. Antigen-specific serum antibodies were measured by ELISA. The mechanism of adjuvant activity of cutaneous CT was also determined.
  
  
  RESULTS
  Sensitization to ALA as measured by allergen-specific IgE occurred by all routes of sensitization and was maximal in response to cutaneous exposure. Sensitization was dependent on CT and did not occur to antigen alone by any route. Mucosal, but not cutaneous, exposure resulted in a robust allergen-specific IgA response. Anaphylaxis occurred in all sensitized groups when orally challenged with ALA. Topical CT induced migration of langerin(neg) dermal dendritic cells to the lymph node, resulting in enhanced proliferation and T(H)2 cytokine production from responder T cells.
  
  
  CONCLUSIONS
  Sensitization can occur via all physiologic routes when adjuvant is present. The skin is a potent and likely important physiologic route of sensitization whereby adjuvant induces an efflux of antigen-bearing dermal dendritic cells to the lymph node that generate a proallergic T(H)2 response.
authors.affiliation: Division of Pediatric Gastroenterology, Mount Sinai School of Medicine, New York, NY 10029, USA. David.dunkin@mssm.edu
authors.forename: David
authors.initials: D
authors.lastname: Dunkin
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Berin
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D007768:Lactalbumin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D007073:Immunoglobulin E; D007768:Lactalbumin