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

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• 作者：Leticia Tordesillas ; PhD^a ; ^b ; Lucie Mondoulet ; PhD^c ; Ana Belen Blazquez ; PhD^a ; ^b ; Pierre-Henri Benhamou ; PhD^c ; Hugh A. Sampson ; MD^a ; ^b ; ^d ; M. Cecilia Berin ; PhD^a ; ^b ; ^d ; ^e ; ^{cecilia.berin@mssm.edu}
• 关键词：Epicutaneous immunotherapy ; oral immunotherapy ; food allergy ; regulatory T cells ; mast cells
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：139
• 期：1
• 页码：189-201.e4
• 全文大小：3873 K
• 卷排序：139

文摘

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.ObjectiveWe sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis.MethodsC3H/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.ResultsBy 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.ConclusionsOur data highlight the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.