title: Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice.
abstract: Epicutaneous immunotherapy onto intact skin has proved to be an efficient and safe alternative treatment of allergy in an animal model with various allergens and in children for cow's milk allergy. The aim of this study was to analyze the different steps of the immunological handling of the allergen when deposited on intact skin using an epicutaneous delivery system and its immune consequences in sensitized BALB/c mice. As expected, when applied on intact skin, OVA exhibits neither a passive passage through the skin nor any detectable systemic delivery. The current study demonstrates that, after a prolonged application on intact skin, OVA is taken up by dendritic cells in the superficial layers of the stratum corneum and transported, after internalization, to the draining lymph nodes, with variations according to the previous level of sensitization of the mice. When OVA is applied with the epicutaneous delivery system repeatedly, specific local and systemic responses are down-modulated in association with the induction of regulatory T cells. Besides providing new insights into skin function in the presence of allergens, this study indicates that the skin might have a tolerogenic role, at least when kept intact.
authors.affiliation: DBV Technologies, Pépinière Paris Santé Cochin, 75014 Paris, France. vincent.dioszeghy@dbv-technologies.com
authors.forename: Vincent
authors.initials: V
authors.lastname: Dioszeghy
authors.forename: Lucie
authors.initials: L
authors.lastname: Mondoulet
authors.forename: Véronique
authors.initials: V
authors.lastname: Dhelft
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ligouis
authors.forename: Emilie
authors.initials: E
authors.lastname: Puteaux
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Benhamou
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
mesh_terms: D000279:Administration, Cutaneous; D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D003888:Desensitization, Immunologic; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007108:Immune Tolerance; D007167:Immunotherapy; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000485:Allergens; D010047:Ovalbumin