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An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium
Open accessAbstract
The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor α stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.
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“Entry of DCs into initial LVs under inflammatory conditions is thus dependent upon integrins and their ligands (109, 110).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [109]
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“This can be explained because ICAM-1 and VCAM-1 are largely absent from LECs under such conditions but are induced by inflammation (109, 110).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [109]
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Metadata
- Authors
- Johnson, L. A., Clasper, S., Holt, A. P., Lalor, P. F., Baban, D., & Jackson, D. G.
- Affiliations
- John Radcliffe Hospital (GB)
- University of Birmingham (GB)
- University of Oxford (GB)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-11-20
- Volume
- 203
- Issue
- 12
- Pages
- 2763-2777
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118156
- OpenAlex
- W2163380226
- Cited by
- 346
- References
- 63
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 20 · 2020: 19 · 2019: 12 · 2018: 17 · 2017: 17 · 2016: 24 · 2015: 14 · 2014: 20 · 2013: 28 · 2012: 16
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Cancer Research UK
- Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Keywords
- leukocyte transmigration, lymphatic endothelium, dermal lymphatic vessels, ICAM-1, VCAM-1, E-selectin, chemokines, dendritic cells, lymph node trafficking, afferent lymphatics, TNF-α, inflammatory cytokines, leukocyte adhesion
- MeSH terms
- Adult, Animals, Cells, Cultured, Dermatitis, Contact, Endothelium, Lymphatic, Humans, Leukocytes, Male, Mice, Inbred BALB C, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Lymphatic Vessels, Mice
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