title: An adjuvant-free mouse model of tree nut allergy using hazelnut as a model tree nut.
abstract: BACKGROUND
  Tree nut allergy, a major group of food allergy, is often linked to fatal or near-fatal systemic anaphylaxis. Currently, an adjuvant-free mouse model to study tree nut hypersensitivity is unavailable. Here we tested the hypothesis that transdermal exposure to hazelnut, a model tree nut, without the use of an adjuvant is sufficient to sensitize mice for immediate hypersensitivity reaction to oral hazelnut challenge.
  
  
  METHODS
  BALB/c mice were repeatedly exposed to hazelnut protein via the transdermal route and systemic allergic and anaphylactic responses were studied.
  
  
  RESULTS
  Transdermal exposure to hazelnut protein elicited robust systemic IgE response in a dose-dependent manner with immunological memory. Oral challenge of transdermally sensitized mice with hazelnut protein resulted in immediate (30 min after the challenge) clinical signs of systemic anaphylaxis as measured by significant clinical scores and drop in rectal temperature. Clinical hypersensitivity reaction was associated with severe pathological changes in the small intestine. Hazelnut-allergic but not control mice exhibited in vivo activation of GATA-3 and hazelnut-driven recall IL-4, IL-5 and IL-13 response by splenocytes, thus elucidating the underlying mechanism of hazelnut allergy development in this model.
  
  
  CONCLUSIONS
  These data suggest that (1) transdermal exposure to hazelnut protein is sufficient to activate the key immune pathways necessary for sensitizing mice for clinical immediate hypersensitivity reactions and (2) this mouse model may be useful for further basic and applied studies on tree nut allergy, especially because it does not depend on an adjuvant for eliciting immediate hypersensitivity reactions to nut protein.
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Nutritional Immunology Program, Michigan State University, East Lansing, Mich. 48823, USA.
authors.forename: Neil Patrick
authors.initials: NP
authors.lastname: Birmingham
authors.forename: Sitaram
authors.initials: S
authors.lastname: Parvataneni
authors.forename: Hanem M Ahmed
authors.initials: HM
authors.lastname: Hassan
authors.forename: Jack
authors.initials: J
authors.lastname: Harkema
authors.forename: Sridhar
authors.initials: S
authors.lastname: Samineni
authors.forename: Lalitha
authors.initials: L
authors.lastname: Navuluri
authors.forename: Caleb James
authors.initials: CJ
authors.lastname: Kelly
authors.forename: Venu
authors.initials: V
authors.lastname: Gangur
mesh_terms: D000276:Adjuvants, Immunologic; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D031211:Corylus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D012639:Seeds / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007073:Immunoglobulin E