Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 6; pp. 1736 - 1751
• Main Authors: Loxham, Matthew, PhD, Davies, Donna E., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017; Elsevier Limited; Mosby
• Subjects: Allergy and Immunology; Animals; Antimicrobial agents; Asthma; Asthma - genetics; Asthma - immunology; Bacteria; Cell surface; Clinical trials; Cluster analysis; cytokine; Cytokines; Disease; Environments; Epithelium; Exposure; Flight corridors; Gene expression; Genetic Predisposition to Disease; Growth factors; Homeostasis; Humans; Hydrocarbons; Immune response; Immune system; Immunomodulation; Inflammation; innate immunity; Ions; Kinases; Macromolecules; Outdoor air quality; Pathogenesis; Pattern recognition; Phenotype; Proteins; Respiratory Mucosa - immunology; Respiratory Mucosa - physiology; Sensors; tight junction; Tissue engineering; Translating; ILC; GWAS; Innate lymphoid cell; Expression quantitative trait locus; Orosomucoid-like 3; BHR; EGFR; Epidermal growth factor receptor; ILC2; SC; Cadherin-related family member 3; DUOX1; innate immunity; Genome-wide association study; SNP; ORMDL3; TLR; GC; PCDH1; Subject cluster; tight junction; Toll-like receptor; cytokine; Dendritic cell; Dual oxidase 1; Gene cluster; TSLP; AJ; GST; AhR; eQTL; Glutathione-S-transferase; Asthma; Adherens junction; homeostasis; Aryl hydrocarbon receptor; Thymic stromal lymphopoietin; Natural killer; TJ; Type 2 innate lymphoid cell; Bronchial hyperresponsiveness; CDHR3; Single nucleotide polymorphism; NK; Protocadherin 1; DC
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2017.04.005

The bronchial epithelium is continuously exposed to a multitude of noxious challenges in inhaled air. Cellular contact with most damaging agents is reduced by the action of the mucociliary apparatus and by formation of a physical barrier that controls passage of ions and macromolecules. In conjunction with these defensive barrier functions, immunomodulatory cross-talk between the bronchial epithelium and tissue-resident immune cells controls the tissue microenvironment and barrier homeostasis. This is achieved by expression of an array of sensors that detect a wide variety of viral, bacterial, and nonmicrobial (toxins and irritants) agents, resulting in production of many different soluble and cell-surface molecules that signal to cells of the immune system. The ability of the bronchial epithelium to control the balance of inhibitory and activating signals is essential for orchestrating appropriate inflammatory and immune responses and for temporally modulating these responses to limit tissue injury and control the resolution of inflammation during tissue repair. In asthmatic patients abnormalities in many aspects of epithelial barrier function have been identified. We postulate that such abnormalities play a causal role in immune dysregulation in the airways by translating gene-environment interactions that underpin disease pathogenesis and exacerbation.