Interactions between innate and adaptive immunity in asthma pathogenesis: New perspectives from studies on acute exacerbations

• Published in: Journal of allergy and clinical immunology Vol. 125; no. 5; pp. 963 - 972
• Main Authors: Holt, Patrick G., DSc, FAA, Strickland, Deborah H., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-05-2010; Elsevier; Elsevier Limited
• Subjects: Adaptive Immunity; Allergens; Allergens - adverse effects; Allergens - immunology; Allergies; Allergy and Immunology; Animals; Asthma; Asthma - immunology; Asthma - physiopathology; atopy; Biological and medical sciences; Bone marrow; Child; Child, Preschool; Chronic obstructive pulmonary disease, asthma; dendritic cells; Dendritic Cells - immunology; Dermatitis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - physiopathology; Immune system; Immunity, Innate; Immunopathology; innate immunity; Medical sciences; Mice; Pneumology; regulatory T cells; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes, Regulatory - immunology; viral infection; Viral infections; Virus Diseases - immunology; Virus Diseases - virology; viral infection; iTreg; Late-phase reaction; Invariant natural killer T; Airway mucosal; LPR; PRR; dendritic cells; innate immunity; Forkhead box protein 3; TLR; FoxP3; iNKT; Toll-like receptor; AEC; Airway epithelial cell; Dendritic cell; TSLP; Pathogen-recognition receptor; atopy; AM; AAM; Asthma; regulatory T cells; Thymic stromal lymphopoietin; Adaptive/inducible regulatory T; Alternatively activated macrophage; DC; Allergy; Lung disease; Immunopathology; Acquired immunity; Respiratory disease; Pathogenesis; Acute; Natural immunity; Atopy; Infection; Exacerbation; Immunology; Antigen presenting cell; Viral disease; T-Lymphocyte; Bronchus disease; Obstructive pulmonary disease; Regulatory cell
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.02.011

Asthma is a complex multigenic disease. The most frequently encountered form is atopic asthma, which is at its highest prevalence during childhood/young adulthood, and this represents the main focus of this review. The primary risk factor for atopic asthma is sensitization to perennial aeroallergens resulting from a failure to generate protective immunologic tolerance. This tolerance process is orchestrated by airway mucosal dendritic cells and normally results in programming of regulatory T cells, which inhibit activation of the TH 2 memory cells that, among other activities, drive IgE production and prime the effector populations responsible for IgE-mediated tissue damage. Emerging evidence highlights the complexity of this process, in particular the iterative nature of the underlying interactions between innate and adaptive immune mechanisms in which virtually every signal emanating from one cellular compartment provokes an answering response from the other. To further complicate this picture, the local mesenchyme can also interpose signals to fine tune immune responses to optimally meet local microenvironmental needs. Perturbation of the balance between these interlinked innate and adaptive immune pathways is increasingly believed to be the basis for disease expression, and in the specific case of atopic asthma, the prototypic example of this (discussed below) is acute exacerbations triggered by viral infections.