Epithelial barrier repair and prevention of allergy
Open accessAbstract
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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FLG degradation products including PCA and UCA are essential for regulation of skin hydration, pH, photoprotection, and normal epidermal barrier function.
“FLG degradation products (FDPs) including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) are essential for the regulation of skin hydration, pH, photoprotection, and normal epidermal barrier function (19, 20).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [19]
Epidermal barrier proteins such as FLG play pivotal roles in maintaining normal skin barrier function.
“Epidermal barrier proteins such as filaggrin (FLG) play pivotal roles in maintaining normal skin barrier function (13, 18, 19).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [19]
Skin barrier dysfunction is considered an initial step of the development of AD.
“In our current study, we focused on PM2.5-mediated skin barrier function directly because skin barrier dysfunction is considered an initial step of the development of AD (14, 19).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [19]
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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.
- Venue
- Journal of Clinical Investigation
- Published
- 2019-02-18
- Volume
- 129
- Issue
- 4
- Pages
- 1463-1474
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- 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 › Physiology › 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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