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Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis
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Background The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD). Objective We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin. Methods We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcεRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris. Results As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although langerin accumulated on the tips of dendrites of activated LCs, FcεRI was expressed diffusely on the cell surfaces on LCs and IDECs in lesional skin from patients with AD. Conclusions These findings highlight interesting differences between LCs and IDECs in epidermis of patients with AD, where LCs, but not IDECs, extend dendrites through the TJs, likely to capture antigens from outside the TJ barrier with a polarized distribution of langerin but not FcεRI. These behavioral differences between skin dendritic cells might reflect an important pathophysiology of AD.
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“The mammalian skin consists of two sets of barriers: one is the stratum corneum and the other is TJs in the stratum granulosum.”
From Morphological characteristics and notes of the skin in preclinical toxicity assessment (2023) · cites this paper as [17]
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“The stratum granulosum contains tight junctions (TJs) that seal intercellular spaces and control the intercellular transport of water, solutes, and water-soluble morecules17.”
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“LCs on the inside of the stratum spinosum can extend their dendrites to outside the TJs in the stratum granulosum to capture antigens17, 19.”
From Morphological characteristics and notes of the skin in preclinical toxicity assessment (2023) · cites this paper as [17]
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Metadata
- Authors
- Yoshida, K., Kubo, A., Fujita, H., Yokouchi, M., Ishii, K., Kawasaki, H., Nomura, T., Shimizu, H., Kouyama, K., Ebihara, T., Nagao, K., & Amagai, M.
- Affiliations
- Keio University (JP)
- Toho University (JP)
- Hokkaido University (JP)
- Corresponding author
- Kubo, Akiharu
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 134
- Issue
- 4
- Pages
- 856-864
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2008105086
- Cited by
- 145
- References
- 51
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 11 · 2021: 11 · 2020: 13 · 2019: 16 · 2018: 13 · 2017: 20 · 2016: 17 · 2015: 6 · 2014: 1
- FWCI
- 16.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Cosmetology Research Foundation
- Japan Society for the Promotion of Science (25670507, 26293259, 26893260, 24390152)
- 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
- Langerhans cells, dendritic epidermal T cells, atopic dermatitis, tight junctions, antigen capture, Langerin, FcεRI, skin barrier, dendritic cell polarization, ichthyosis vulgaris, plaque psoriasis
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Dendritic Cells, Dermatitis, Atopic, Epidermis, Humans, Langerhans Cells, Microscopy, Electron, Scanning, Organ Culture Techniques, Psoriasis, Antigens, CD, Ichthyosis Vulgaris, Receptors, IgE, Antigen Presentation, Tight Junctions, Lectins, C-Type, Mannose-Binding Lectins, Mice, Transcriptome
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