External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers
Open accessAbstract
Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
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Langerhans cells on the inside of the stratum spinosum can extend their dendrites to outside the tight junctions in the stratum granulosum to capture antigens.
“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 [19]
The Results and Discussion sections report that activated Langerhans cells extend dendrites through tight junctions in the stratum granulosum and take up antigens beyond the barrier. The paper describes LC cell bodies in the deep epidermis, but the passages do not specifically place them in the stratum spinosum. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe mammalian skin consists of two sets of barriers: the stratum corneum and tight junctions in the stratum granulosum.
“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 [19]
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- Authors
- Kubo, A., Nagao, K., Yokouchi, M., Sasaki, H., & Amagai, M.
- Affiliations
- Keio University (JP)
- Jikei University School of Medicine (JP)
- Corresponding author
- Kubo, Akiharu
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-12-07
- Volume
- 206
- Issue
- 13
- Pages
- 2937-2946
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2806471
- OpenAlex
- W2169192341
- Cited by
- 491
- References
- 0
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 20 · 2023: 25 · 2022: 30 · 2021: 26 · 2020: 34 · 2019: 32 · 2018: 30 · 2017: 46 · 2016: 39 · 2015: 29 · 2014: 37 · 2013: 29 · 2012: 38
- FWCI
- 17.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21229014)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Langerhans cells, antigen uptake, tight junctions, skin barrier, stratum corneum, keratinocytes, dendrite elongation, Langerin, Birbeck granules, claudins, tricellular tight junctions, skin immunity, antigen sampling
- MeSH terms
- Animals, Antigens, Endocytosis, Epidermis, Female, Langerhans Cells, Mice, Inbred C57BL, Ovalbumin, Tight Junctions, Imaging, Three-Dimensional, Mice
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