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The use of biologics for immune modulation in allergic disease
Willem van de Veen, Mübeccel Akdis
Willem van de Veen, Mübeccel Akdis
Published March 18, 2019
Citation Information: J Clin Invest. 2019;129(4):1452-1462. https://doi.org/10.1172/JCI124607.
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Review Series

The use of biologics for immune modulation in allergic disease

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Abstract

The rising prevalence of allergies represents an increasing socioeconomic burden. A detailed understanding of the immunological mechanisms that underlie the development of allergic disease, as well as the processes that drive immune tolerance to allergens, will be instrumental in designing therapeutic strategies to treat and prevent allergic disease. Improved characterization of individual patients through the use of specific biomarkers and improved definitions of disease endotypes are paving the way for the use of targeted therapeutic approaches for personalized treatment. Allergen-specific immunotherapy and biologic therapies that target key molecules driving the Th2 response are already used in the clinic, and a wave of novel drug candidates are under development. In-depth analysis of the cells and tissues of patients treated with such targeted interventions provides a wealth of information on the mechanisms that drive allergies and tolerance to allergens. Here, we aim to deliver an overview of the current state of specific inhibitors used in the treatment of allergy, with a particular focus on asthma and atopic dermatitis, and provide insights into the roles of these molecules in immunological mechanisms of allergic disease.

Authors

Willem van de Veen, Mübeccel Akdis

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Figure 1

Key cellular and molecular players in allergic sensitization.

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Key cellular and molecular players in allergic sensitization.
Allergens ...
Allergens and pathogens that have passed the skin or mucosal epithelium are phagocytosed by antigen-presenting cells (APCs). These APCs mature as a result of cytokines produced by epithelial cells, then migrate to draining lymph nodes, where they present allergen-derived peptides to CD4+ T cells and induce differentiation to Th2 cells. ILC2s are also activated by epithelial cell–derived cytokines such as IL-25, IL-33, and TSLP. Th2 cells and ILC2s produce type 2 cytokines such as IL-4, IL-13, IL-5, and IL-9. IL-4 and IL-13 drive IgE class switch recombination of B cells, leading to allergen-specific IgE production. Allergen-specific IgE binds to FcεRI on mast cells and basophils. IL-4, IL-9, and IL-13 promote mucus secretion by goblet cells, whereas IL-5 is instrumental in eosinophil recruitment. TCR, T cell receptor.
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