Epithelial barrier repair and prevention of allergy
Elena Goleva,1 Evgeny Berdyshev,2 and Donald Y.M. Leung1,3
1Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, and
2Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
3Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
Address correspondence to: Donald Y.M. Leung, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA. Phone: 303.398.1379; Email: Leungd@NJHealth.org.
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1Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, and
2Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
3Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
Address correspondence to: Donald Y.M. Leung, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA. Phone: 303.398.1379; Email: Leungd@NJHealth.org.
Find articles by Berdyshev, E. in: JCI | PubMed | Google Scholar
1Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, and
2Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
3Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
Address correspondence to: Donald Y.M. Leung, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA. Phone: 303.398.1379; Email: Leungd@NJHealth.org.
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Leung, D.
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PubMed
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First published February 18, 2019 - More info
J Clin Invest. 2019;129(4):1463–1474. https://doi.org/10.1172/JCI124608.
© 2019 American Society for Clinical Investigation
Allergic diseases have in common a dysfunctional epithelial barrier, which allows the penetration of allergens and microbes, leading to the release of type 2 cytokines that drive allergic inflammation. The accessibility of skin, compared with lung or gastrointestinal tissue, has facilitated detailed investigations into mechanisms underlying epithelial barrier dysfunction in atopic dermatitis (AD). This Review describes the formation of the skin barrier and analyzes the link between altered skin barrier formation and the pathogenesis of AD. The keratinocyte differentiation process is under tight regulation. During epidermal differentiation, keratinocytes sequentially switch gene expression programs, resulting in terminal differentiation and the formation of a mature stratum corneum, which is essential for the skin to prevent allergen or microbial invasion. Abnormalities in keratinocyte differentiation in AD skin result in hyperproliferation of the basal layer of epidermis, inhibition of markers of terminal differentiation, and barrier lipid abnormalities, compromising skin barrier and antimicrobial function. There is also compelling evidence for epithelial dysregulation in asthma, food allergy, eosinophilic esophagitis, and allergic rhinosinusitis. This Review examines current epithelial barrier repair strategies as an approach for allergy prevention or intervention.
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Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)