title: Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model.
abstract: BACKGROUND
  Allergy to cow's milk increases the risk of sensitization to other foods in young children.
  
  
  OBJECTIVE
  We sought to evaluate the effect of early epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house dust mite (HDM) in a murine model of sensitization to cow's milk.
  
  
  METHODS
  BALB/c mice orally sensitized to milk were epicutaneously treated with a Viaskin patch (DBV Technologies) loaded with milk proteins for 8 weeks. Mice were then sensitized to peanut or HDM. After sensitization to peanut, mice were exposed to a peanut regimen known to induce eosinophilic esophageal inflammation. After sensitization to HDM, mice were challenged with aerosols to HDM, and airway hyperresponsiveness was evaluated by using plethysmography. Humoral response was also analyzed. The role of regulatory T (Treg) cells was evaluated by adoptively transferring Treg cells from milk EPIT-treated mice to naive mice before sensitization to peanut. Protection against anaphylaxis was also investigated. Methylation of the promoter region of transcription factors was analyzed by using PCR assays.
  
  
  RESULTS
  In milk-sensitized mice specific EPIT prevented further sensitization to peanut or HDM. EPIT significantly modified the humoral response, reduced TH2 cytokine levels, decreased eosinophilic esophageal infiltration, and suppressed airway hyperresponsiveness. The protective effect was sustained over 2 months. Moreover, the adoptive transfer of milk EPIT Treg cells completely prevented sensitization to peanut and peanut-induced anaphylaxis. Milk EPIT enhanced methylation of the GATA-3 promoter region.
  
  
  CONCLUSIONS
  Our results showed that EPIT influences the natural history of allergy and reduces the risk of further sensitization through a Treg cell-dependent mechanism.
authors.affiliation: DBV Technologies, Bagneux, France. Electronic address: lucie.mondoulet@dbv-technologies.com.
authors.forename: Lucie
authors.initials: L
authors.lastname: Mondoulet
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dioszeghy
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Puteaux
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ligouis
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dhelft
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Plaquet
authors.affiliation: Université Paris Descartes-Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
authors.affiliation: DBV Technologies, Bagneux, France.
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Benhamou
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D000818:Animals; D010367:Arachis / Q000737:chemistry / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D002648:Child; D056738:Cross Protection; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016269:Milk Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008894:Milk Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D010991:Plethysmography; D011401:Promoter Regions, Genetic; D039981:Pyroglyphidae / Q000737:chemistry / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: D000485:Allergens; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D008894:Milk Proteins
keywords: Allergy; epicutaneous immunotherapy; food allergy; milk; peanut; prevention; treatment