Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice

The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy.After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin？ (DBV Technologies, Paris) applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response.EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (2.7？±？0.9, compared to Sham 19.9？±？1.5, p？<？0.01), mRNA expression of Th2 cytokines in tissue and intestinal villus sub-atrophia (2.9？±？0.2 vs Sham, 2.1？±？0.2, p？<？0.05). By contrast, EPIT on stripped skin reinforced Th2 systemic immunological response as well as eosinophil infiltration (26.8？±？15.1), mRNA expression of Th2 cytokines and duodenal villus/crypt-ratio (2.4？±？0.3).Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.A new method of allergen-specific immunotherapy, via the epicutaneous route (epicutaneous immunotherapy, EPIT), is currently under investigation, using a unique epicutaneous delivery system (Viaskin？, DBV Technologies, Paris, France) consisting of a central transparent plastic membrane (11 mm in diameter) of polyethylene electrically charged with electrostatic forces and an adhesive sheath of nonwoven film. Dry powder of proteins is maintained on the backing by electrostatic forces. An occlusive chamber is created on the skin that rapidly generates moisture and releases the allergen from its support. The allergen is then absorbe