Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions
Open accessAbstract
House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.
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The expression of subunit proteins such as claudins and occludins is reduced by exposure to allergens and staphylococcal strains, compromising barrier integrity in AD.
“The expression of subunit proteins such as claudins and occludins is reduced by exposure to allergens and staphylococcal strains, compromising barrier integrity in AD.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [46]
The Discussion reports that exposure to the dust-mite allergen Der p 1 decreased occludin and ZO-1 in epithelial cells while increasing permeability. It reports cleavage of claudin-1 peptides, not reduced expression of claudin proteins. The paper does not establish these effects for staphylococcal strains or in atopic dermatitis (AD). (LLM, conf=0.88)
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References 57 · Cited by 775
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- Authors
- Wan, H., Winton, H. L., Soeller, C., Tovey, E. R., Gruenert, D. C., Thompson, P. J., Stewart, G. A., Taylor, G. W., Garrod, D. R., Cannell, M. B., & Robinson, C.
- Affiliations
- St George's Hospital (GB)
- The University of Sydney (AU)
- University of California, San Francisco (US)
- The University of Western Australia (AU)
- St George's, University of London (GB)
- University of Manchester (GB)
- Corresponding author
- Robinson, Clive
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1999-07-01
- Volume
- 104
- Issue
- 1
- Pages
- 123-133
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408401
- OpenAlex
- W1996955331
- Cited by
- 775
- References
- 57
- Citations by year
- 2026: 25 · 2025: 23 · 2024: 28 · 2023: 31 · 2022: 24 · 2021: 31 · 2020: 21 · 2019: 15 · 2018: 26 · 2017: 44 · 2016: 27 · 2015: 30 · 2014: 34 · 2013: 30 · 2012: 34
- FWCI
- 12.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- Der p 1, house dust mite allergens, Dermatophagoides pteronyssinus, tight junction disruption, claudin-1, cysteine protease, epithelial permeability, paracellular pathway, allergen sensitization, asthma, airway epithelium
- MeSH terms
- Allergens, Animals, Antipain, Biological Transport, Cell Line, Cells, Cultured, Cysteine Endopeptidases, Desmosomes, Dogs, Enzyme Inhibitors, Epithelium, Glycoproteins, Humans, Image Processing, Computer-Assisted, Kidney, Membrane Proteins, Mites, Peptide Fragments, Permeability, Rhinitis, Allergic, Perennial, Substrate Specificity, Tight Junctions, Antigens, Dermatophagoides, Claudin-1, Occludin
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