Cited by 378Dermatology and Skin DiseasesContact Dermatitis and AllergiesAdvancements in Transdermal Drug Delivery

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Open access
Kubo, Akiharu, Nagao, Keisuke, Amagai, Masayuki·2012·Journal of Clinical Investigation

Abstract

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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Crossref · 10.1172/jci57416

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129 of 129 references verified0 citation errors · 0 not checkable

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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)

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  • Perturbed 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].”

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Research works printed but not linked: 7

  1. [42]Niess JH, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science . 2005;307(5707):254-258.
  2. [49]Lessard RJ, Wolff K, Winkelmann RK. The disappearance and regeneration of Langerhans cells following epidermal injury. J Invest Dermatol . 1968;50(2):171-179.
  3. [45]J Allergy Clin Immunol . 2007;119(4):982-990.
  4. [80]Sundberg JP. The flaky tail (ft) mutation. In: Sundberg JP, ed. Handbook of Mouse Mutations with Skin and Hair Abnormalities. Animal Models and Biochemical Tools . Vol. 2. Ann Arbor, Michigan, USA: CRC Press; 1984:269-273.
  5. Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat Genet . 2005;37(1):56-65.
  6. [99]Matsui T, et al. Skin-specific aspartic protease SASPase regulate stratum corneum hydration through profilaggrin processing. EMBO Mol Med . 2011;3(6):320-333.
  7. [117]Gutowska-Owsiak D, Schaupp AL, Salimi M, Taylor S, Ogg GS. Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. Br J Dermatol . 2011; 165(3):492-498.

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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)
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
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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