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

Lucie Mondoulet; Sophie Wavrin; Vincent Dioszeghy; Véronique Dhelft; Emilie Puteaux; Mélanie Ligouis; Camille Plaquet; Christophe Dupont; Pierre-Henri Benhamou; Lucie Mondoulet; Sophie Wavrin; Vincent Dioszeghy; Véronique Dhelft; Emilie Puteaux; Mélanie Ligouis; Camille Plaquet; Christophe Dupont; Pierre-Henri Benhamou

doi:10.3934/Allergy.2017.1.1

AIMS Allergy and Immunology

2017, Volume 1, Issue 1: 1-14. doi: 10.3934/Allergy.2017.1.1

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Research article

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

1.
DBV Technologies, Montrouge, France
2.
Université Paris Descartes-Hôpital Necker-Enfants Malades, Paris, France

Received: 17 November 2016 Accepted: 08 March 2017 Published: 15 March 2017

Background: Epicutaneous immunotherapy (EPIT^®), currently investigated in the treatment of food allergy, needs the integrity of the skin to warrant safety and efficacy. Mutations in the gene encoding the key epidermal protein filaggrin (FLG) are risk factors for peanut allergy and disrupt the skin intergrity. We investigated the association between FLG deficiency and peanut EPIT^® 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®, using Viaskin^®, 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 biaised immunological responses. In sensitized mice, EPIT^®significantly reduced IgE levels, splenocytes 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^highDCs, which migrated to afferent lymph nodes, as already described in WT mice. Conclusions: EPIT^®was efficient and safe in FLG-/- mice, suggesting that in Humans EPIT^® keeps efficacy and safety in the presence of loss of function of FLG.
- allergy,
- epicutaneous immunotherapy,
- filaggrin,
- skin,
- atopic dermatitis
Citation: Lucie Mondoulet, Sophie Wavrin, Vincent Dioszeghy, Véronique Dhelft, Emilie Puteaux, Mélanie Ligouis, Camille Plaquet, Christophe Dupont, Pierre-Henri Benhamou. No impact of filaggrin deficiency on the efficacy of epicutaneous immunotherapy in a murine model[J]. AIMS Allergy and Immunology, 2017, 1(1): 1-14. doi: 10.3934/Allergy.2017.1.1

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Abstract

Background: Epicutaneous immunotherapy (EPIT^®), currently investigated in the treatment of food allergy, needs the integrity of the skin to warrant safety and efficacy. Mutations in the gene encoding the key epidermal protein filaggrin (FLG) are risk factors for peanut allergy and disrupt the skin intergrity. We investigated the association between FLG deficiency and peanut EPIT^® 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®, using Viaskin^®, 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 biaised immunological responses. In sensitized mice, EPIT^®significantly reduced IgE levels, splenocytes 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^highDCs, which migrated to afferent lymph nodes, as already described in WT mice. Conclusions: EPIT^®was efficient and safe in FLG-/- mice, suggesting that in Humans EPIT^® keeps efficacy and safety in the presence of loss of function of FLG.

References

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