Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis. 2016

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



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.


We sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis.


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.


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.


Our data highlight the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.

Link To:

Tordesillas L1, Mondoulet L2, Blazquez AB1, Benhamou PH2, Sampson HA3, Berin MC4.

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

J Allergy Clin Immunol. 2016 Jun 11. pii: S0091-6749(16)30429-8. doi: 10.1016/j.jaci.2016.03.057.





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