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Mechanisms of immune tolerance to allergens


Fujita, Hiroyuki; Meyer, Norbert; Akdis, Mübeccel; Akdis, Cezmi A (2012). Mechanisms of immune tolerance to allergens. Chemical Immunology and Allergy, 96:30-38.

Abstract

In allergic diseases, immune responses are induced by normally well-tolerated allergens, which result in chronic inflammation characterized by antibody secretion and T cell activation. For almost 100 years, allergen-specific immunotherapy (allergen-SIT) has been the potentially curative and antigen-specific method for the treatment of allergic diseases. Allergen-SIT alters the course of allergic diseases and can reduce allergic symptoms and medication use. The key mechanism behind allergen-SIT is the induction of peripheral T cell tolerance by altering the balance between Th cells and regulatory T cells. Both naturally occurring thymus-derived FOXP3(+)CD4(+)CD25(+) regulatory T cells and inducible type 1 regulatory T cells suppress the development of allergic diseases via several mechanisms including suppression of dendritic cells, Th cells, mast cells, eosinophils and basophils; suppression of inflammatory cell migration to tissues; and decrease of the ratio between allergen-specific IgE and IgG4 antibodies. These effects are mainly mediated by the suppressive cytokines IL-10 and TGF-β. Knowledge of this molecular basis is crucial to understanding the regulation of the immune response and their possible therapeutic applications for allergic diseases.

Abstract

In allergic diseases, immune responses are induced by normally well-tolerated allergens, which result in chronic inflammation characterized by antibody secretion and T cell activation. For almost 100 years, allergen-specific immunotherapy (allergen-SIT) has been the potentially curative and antigen-specific method for the treatment of allergic diseases. Allergen-SIT alters the course of allergic diseases and can reduce allergic symptoms and medication use. The key mechanism behind allergen-SIT is the induction of peripheral T cell tolerance by altering the balance between Th cells and regulatory T cells. Both naturally occurring thymus-derived FOXP3(+)CD4(+)CD25(+) regulatory T cells and inducible type 1 regulatory T cells suppress the development of allergic diseases via several mechanisms including suppression of dendritic cells, Th cells, mast cells, eosinophils and basophils; suppression of inflammatory cell migration to tissues; and decrease of the ratio between allergen-specific IgE and IgG4 antibodies. These effects are mainly mediated by the suppressive cytokines IL-10 and TGF-β. Knowledge of this molecular basis is crucial to understanding the regulation of the immune response and their possible therapeutic applications for allergic diseases.

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16 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:04 Jun 2012 07:11
Last Modified:15 Jul 2016 07:30
Publisher:Karger
ISSN:0079-6034
Publisher DOI:https://doi.org/10.1159/000331868
PubMed ID:22433368

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