Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis

Leticia Tordesillas, Lucie Mondoulet, Ana Belen Blazquez, Pierre Henri Benhamou, Hugh A. Sampson, M. Cecilia Berin

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Background The attempt to induce oral tolerance as a treatment for food allergy has been hampered by a lack of sustained clinical protection. Immunotherapy by nonoral routes, such as the skin, may be more effective for the development of maintained tolerance to food allergens. Objective We sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis. Methods C3H/HeJ mice were sensitized to ovalbumin (OVA) orally or through the skin and treated with EPIT using OVA-Viaskin patches or oral immunotherapy using OVA. Mice were orally challenged with OVA to induce anaphylaxis. Antigen-specific regulatory T (Treg)-cell induction was assessed by flow cytometry using a transgenic T-cell transfer model. Results By using an adjuvant-free model of food allergy generated by epicutaneous sensitization and reactions triggered by oral allergen challenge, we found that EPIT induced sustained protection against anaphylaxis. We show that the gastrointestinal tract is deficient in de novo generation of Treg cells in allergic mice. This defect was tissue-specific, and epicutaneous application of antigen generated a population of gastrointestinal-homing LAP+Foxp3 Treg cells. The mechanism of protection was found to be a novel pathway of direct TGF-β–dependent Treg-cell suppression of mast cell activation, in the absence of modulation of T- or B-cell responses. Conclusions Our data highlight the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.

Original languageEnglish
Pages (from-to)189-201.e4
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - 1 Jan 2017


  • Epicutaneous immunotherapy
  • food allergy
  • mast cells
  • oral immunotherapy
  • regulatory T cells


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