Environmental factors in epithelial barrier dysfunction

The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment—the exposome—have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis. The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment—the exposome—have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis. The epithelial tissue acts as a barrier by forming a continuous layer with almost no intracellular gaps and protects the body from environmental stress, physical and chemical damage, infections, and allergens. The structure and the function of the epithelial barrier differs between the skin, the gastrointestinal system, and the respiratory tract, which are the main interfaces between the host and the environment.1Loxham M. Davies D.E. Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients.J Allergy Clin Immunol. 2017; 139: 1736-1751Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar,2Moens E. Veldhoen M. Epithelial barrier biology: good fences make good neighbours.Immunology. 2012; 135: 1-8Crossref PubMed Scopus (0) Google Scholar The skin barrier is multicellular, stratified, tight, and defensive. Stratum corneum forms the upper layer with a physical thickness and strength. 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Several waves of threats to the health of all living beings, particularly humans and domestic animals, occurred with extensive decrease in air quality in cities with increases in particulate matter (PM), diesel exhaust, ozone, and cigarette smoke, increases in the toxic burden caused by cleaning products, detergents, and surfactants, increases in processed foods and use of emulsifiers, and the introduction of nanoparticles (NPs) and microplastics, all of which together significantly increased the health burden caused by environmental exposure within a couple of decades, particularly after the 1960s (Table I). Early studies on epithelial barrier were performed on gut barrier and its link to inflammatory bowel and celiac diseases.6Schulzke J.D. Fromm M. Zeitz M. Menge H. Riecken E.O. Bentzel C.J. Tight junction regulation during impaired ion transport in blind loops of rat jejunum.Res Exp Med (Berl). 1990; 190: 59-68Crossref PubMed Google Scholar, 7Schulzke J.D. Riecken E.O. 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This rostrum highlights the effects of environmental factors such as protease allergen enzymes, detergents, tobacco smoke and e-cigarettes, ozone, PM, NPs, emulsifiers, and micro and nanoplastics on the integrity of the epithelial barriers.Table IEnvironmental factors and epithelial barrierEnvironmental factorMechanismReferenceProtease allergens•Elicit non-IgE–mediated reactions via proteinase-activated receptors•Degrade barrier proteins•Increase epithelial permeability55Matsumura Y. Role of allergen source-derived proteases in sensitization via airway epithelial cells.J Allergy (Cairo). 2012; 2012903659Crossref PubMed Google Scholar,57Takai T. Ikeda S. Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases.Allergol Int. 2011; 60: 25-35Abstract Full Text PDF PubMed Scopus (81) Google Scholar, 58Wan H. Winton H.L. Soeller C. Taylor G.W. Gruenert D.C. 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Bay B.H. et al.Targeted metabolomics reveals differential biological effects of nanoplastics and nanoZnO in human lung cells.Nanotoxicology. 2019; 13: 1117-1132Crossref PubMed Scopus (4) Google ScholarPM10, PM with diameter <2.5 μm. Open table in a new tab PM10, PM with diameter <2.5 μm. Epithelial tissues are organized according to the needs of the tissues, providing a strong physical barrier in the skin, continuous particle clearance for a healthy gas exchange in the lungs, and extensive nutrient and water exchange in the gastrointestinal system, simultaneously providing protection against microbes, toxins, and the environmental exposome with overall, physical, chemical, and immunologic barrier functions.25Agache I. Miller R. Gern J.E. Hellings P.W. Jutel M. Muraro A. et al.Emerging concepts and challenges in implementing the exposome paradigm in allergic diseases and asthma: a PRACTALL document.Allergy. 2019; 74: 449-463Crossref PubMed Scopus (20) Google Scholar Alignment of epithelial cells differs depending on their location in the body and their role. The physical barrier of the skin consists of a large number of epidermal layers and keratinocytes. Stratum corneum, the outermost layer, consists of many layers of corneocytes and lamellar bodies between them to form a thick, strong, and protective barrier.3Ega