No impact of filaggrin deficiency on the efficacy of epicutaneous immunotherapy in a murine model

Background: Epicutaneous immunotherapy (EPIT (R)), is currently being investigated for the treatment of food allergy, utilizes intact skin to activate the immune system. Mutations in the gene encoding the key epidermal protein filaggrin (FLG) are risk factors for peanut allergy and disrupt the skin integrity. We investigated the association between FLG deficiency and peanut EPIT (R) efficacy in a murine model. Methods: FLG mutant mice deficient in filaggrin (FLG-/-) or wild-type (WT) mice were sensitized with peanut protein extract (peanut protein) and cholera toxin. Sensitized mice received a patch per week during 8 weeks for EPIT (R), using Viaskin (R), and were then submitted to sustained peanut oral exposure. We assessed blood humoral and cellular responses and evaluated eosinophil infiltration in the gut mucosa. The different steps of allergen capture and transportation following deposition on the skin was also analyzed in sensitized mice. Results: Sensitization of mice was confirmed by a significant increase of specific Th2 biased immunological responses. In sensitized mice, EPIT (R) significantly reduced IgE levels, splenocyte secretion of Th2 cytokines and recruitment of eosinophils in esophagus, compared to sensitized mice without epicutaneous immunotherapy. The allergen applied onto the skin of FLG-/- mice did not undergo passive skin passage or systemic delivery. Instead, the allergen was captured by skin CD205(high) DCs, which migrated to afferent lymph nodes, as already described in WT mice. Conclusions: EPIT (R) was efficient and safe in FLG-/- mice, suggesting that in humans, the efficacy and safety observed with EPIT (R) is maintained in the presence of loss of function of FLG.