Cited by 251Dermatology and Skin DiseasesContact Dermatitis and AllergiesAsthma and respiratory diseases

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Epithelial barrier repair and prevention of allergy

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Goleva, Elena, Berdyshev, Evgeny, Leung, Donald Y.M.·2019·Journal of Clinical Investigation

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Abstract

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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Authors: Goleva, E., Berdyshev, E., & Leung, D. Y. M.
Affiliations: National Jewish Health (US)
University of Colorado Denver (US)
Corresponding author: Leung, Donald Y.M.
ORCID: Goleva, Elena
Berdyshev, Evgeny
Leung, Donald Y.M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2019-02-18
Volume: 129
Issue: 4
Pages: 1463-1474
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci124608
PMC: PMC6436854
OpenAlex: W2911342375
Cited by: 251
References: 220
Citations by year: 2026: 17 · 2025: 48 · 2024: 43 · 2023: 43 · 2022: 27 · 2021: 31 · 2020: 35 · 2019: 6
FWCI: 4.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Jewish Health
National Institutes of Health (RR025780, AR41256)
National Institute of Allergy and Infectious Diseases (U19AI117673, AI117673, AR41256, U01AI147462)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 41256, R01AR041256, R01 AR41256)
National Center for Research Resources (RR-025780, UL1RR025780)
Topics: Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Keywords: epithelial barrier repair, allergic diseases, atopic dermatitis, skin barrier formation, keratinocyte differentiation, stratum corneum, type 2 cytokines, asthma, food allergy, eosinophilic esophagitis, allergic rhinosinusitis, allergen penetration, antimicrobial activity, allergy prevention
MeSH terms: Allergens, Animals, Cell Differentiation, Epidermis, Humans, Hypersensitivity, Inflammation, Keratinocytes

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Epithelial barrier repair and prevention of allergy

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