title: Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.
abstract: BACKGROUND
  Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes.
  
  
  METHODS
  Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure.
  
  
  RESULTS
  Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2)) and reduced villus/crypt ratios (1.6±0.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm(2), p<0.05), mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05), IL-5 (p<0.05), and IL-13 (p<0.05)--GATA-3 (p<0.05), and intestinal villus sub-atrophia (2.3±0.15). EPIT also increased specific IgG2a (p<0.05) and mRNA expression of Foxp3 (p<0.05) in the esophageal mucosa.
  
  
  CONCLUSIONS
  Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.
authors.affiliation: DBV Technologies, Pépinière Santé Paris Cochin, Paris, France. lucie.mondoulet@dbv-technologies.com
authors.forename: Lucie
authors.initials: L
authors.lastname: Mondoulet
authors.forename: Vincent
authors.initials: V
authors.lastname: Dioszeghy
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ligouis
authors.forename: Véronique
authors.initials: V
authors.lastname: Dhelft
authors.forename: Emilie
authors.initials: E
authors.lastname: Puteaux
authors.forename: Yan
authors.initials: Y
authors.lastname: Cherel
authors.forename: Franck
authors.initials: F
authors.lastname: Letourneur
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Benhamou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D010367:Arachis / Q000009:adverse effects; D003888:Desensitization, Immunologic / Q000379:methods*; D004066:Digestive System Diseases / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D021183:Peanut Hypersensitivity / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*; D013154:Spleen / Q000276:immunology