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Mechanisms of tolerance induction in allergic disease: integrating current and emerging concepts.
MedLine Citation:
PMID:  23331558     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The prevalence of atopy and allergic disease continues to escalate worldwide. Defining immune mechanisms that suppress the underlying Th2-driven inflammatory process is critical for the rational design of new treatments to prevent or attenuate disease. Allergen immunotherapy has provided a useful framework for evaluating changes in the immune response that occur during the development of tolerance. Despite this, elucidating the phenotypic and functional properties of regulatory cells, has proven challenging in humans with allergic disease. This article provides an overview of our current understanding of the immune pathways that orchestrate allergen tolerance, with an emphasis on emerging concepts related to human disease. A variety of regulatory cell types, including IL-10-secreting T and B cells, play a pivotal role in suppressing allergic responses to inhaled, ingested and injected allergens. These cells may inhibit Th2 effectors directly, or else indirectly, through other cell types and mediators. Protective antibodies, including IgG4, Fc sialylated IgG, and IgA, have the capacity to modulate the response by preventing allergen binding to surface-bound IgE, or inhibiting dendritic cell maturation. Immune cell plasticity may augment suppression of Th2 cells by T regulatory cells, through mechanisms that involve T cell conversion, or else unconventional roles of classical effector cells. These actions depend upon external cues provided by the in vivo milieu. As such, specific anatomical sites may preferentially favour tolerance induction. Recent scientific advances now allow a global analysis of immune parameters that capture novel markers of tolerance induction in allergic patients. Such markers could provide new molecular targets for assessing tolerance, and for designing treatments that confer long-lasting protection in a safe and efficacious fashion.
Authors:
J Wisniewski; R Agrawal; J A Woodfolk
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  43     ISSN:  1365-2222     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  164-76     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
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