Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases
Open accessAbstract
Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases.
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Either too much or too little EGFR activity at TJs will impair barrier function and alter cytokine expression, both of which contribute to skin inflammatory skin diseases as well as skin cancer.
“Either too much or too little EGFR activity at TJs will impair barrier function and alter cytokine expression, both of which contribute to skin inflammatory skin diseases3 as well as skin cancer54.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [3]
The discussion of TJ barriers (p. 5) links impaired tight-junction function to epidermal barrier defects and possible atopic dermatitis, and Figure 2 (p. 4) describes cytokine production after barrier damage. Neither passage supports the specific claim that too much or too little EGFR activity at TJs causes those effects. Skin cancer is attached to a different citation in the citing sentence and is not judged here. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPerturbed barrier function is critical for the development of atopic dermatitis and other allergic disorders, namely atopic march.
“Perturbed barrier function is critical for the development of not only atopic dermatitis but also other allergic disorders, namely, atopic march [8,9,10,11].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [9]
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- Authors
- Kubo, A., Nagao, K., & Amagai, M.
- Affiliations
- Keio University (JP)
- Corresponding author
- Amagai, Masayuki
- Venue
- Journal of Clinical Investigation
- Published
- 2012-02-01
- Volume
- 122
- Issue
- 2
- Pages
- 440-447
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3266780
- OpenAlex
- W2157038335
- Cited by
- 378
- References
- 129
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 21 · 2023: 21 · 2022: 25 · 2021: 24 · 2020: 28 · 2019: 26 · 2018: 21 · 2017: 32 · 2016: 30 · 2015: 26 · 2014: 41 · 2013: 34 · 2012: 16
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (22249044, 21229014)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- skin barrier dysfunction, skin sensitization, atopic dermatitis, atopic diseases, filaggrin mutations, stratum corneum, tight junctions, asthma, allergic rhinitis, food allergy, skin barrier
- MeSH terms
- Filaggrin Proteins, Animals, Dermatitis, Atopic, Epidermis, Humans, Hypersensitivity, Immediate, Intermediate Filament Proteins, Mutation, Skin
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