Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis - 18/04/17
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Epicutaneous immunotherapy, oral immunotherapy, food allergy, regulatory T cells, mast cells
Abbreviations used : CT, EPIT, LAP, MLN, OIT, Treg
Plan
Graphical abstract printed with permission from Mount Sinai Health System. Figure created by Jill K. Gregory, CMI. |
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This study was supported by the National Institutes of Health (grant no. AI093577 to M.C.B.), David H. and Julia Koch Research Program in Food Allergy Therapeutics (to H.A.S.), and Robin Chemers Neustein Fellowship (to L.T.). |
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Disclosure of potential conflict of interest: L. Tordesillas received travel support from DBV Technologies (the developer and owner of the Viaskin patch) to present this work in part at the European Academy of Allergy and Clinical Immunology. L. Mondoulet is an employee of DBV Technologies and receives research support, support for travel, and payment for writing or reviewing the manuscript from DBV Technologies. P.-H. Benhamou is CEO of DBV Technologies, serves on the board, and receives research support, travel support, and stock options. H. A. Sampson receives research support from the National Institute of Allergy and Infectious Diseases (NIAID); serves as a consultant for Allertein Therapeutics, LLC, Genentech, Sanofi, Stallergens, and Merck; is an employee of DBV Technologies as Chief Scientific Officer; and holds stock options in Allertein Therapeutics and DBV Therapeutics. M. C. Berin receives research support from the NIAID and receives travel support from DBV Technologies. A. B. Blazquez declares that she has no relevant conflicts of interest. |
Vol 139 - N° 1
P. 189 - janvier 2017 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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