Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1
Abstract
Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8 + T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.
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LYVE-1, concentrated in LEC flaps of initial LVs, participates in DC entry into the vessel lumen.
“LYVE-1, which is concentrated in LEC flaps of initial LVs, participates in DC entry into the vessel lumen (115).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [115]
DCs engage LYVE-1 through a hyaluronan bridge involving simultaneous binding of hyaluronan to LYVE-1 on the LEC and CD44 on the DC.
“DCs engage LYVE-1 through a hyaluronan bridge that involves the simultaneous binding of hyaluronan to LYVE-1 on the LEC and CD44 on the DC (115, 116) ( Figure 3b ).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [115]
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References 50 · Cited by 197
- Authors
- Johnson, L. A., Banerji, S., Lawrance, W., Gileadi, U., Prota, G., Holder, K. A., Roshorm, Y. M., Hanke, T., Cerundolo, V., Gale, N. W., & Jackson, D. G.
- Affiliations
- John Radcliffe Hospital (GB)
- King Mongkut's University of Technology Thonburi (TH)
- University of Oxford (GB)
- Regeneron (United States) (US)
- Corresponding author
- Johnson, Louise A
- Jackson, David G
- ORCID
- Venue
- Nature Immunology
- Published
- 2017-05-15
- Volume
- 18
- Issue
- 7
- Pages
- 762-770
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2614673842
- Cited by
- 197
- References
- 50
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 31 · 2023: 22 · 2022: 21 · 2021: 30 · 2020: 19 · 2019: 18 · 2018: 21 · 2017: 6
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (17722, 11331)
- Medical Research Council (MR/N023668/1, MR/L008610/1, MC_UU_00008/2, MC_UU_00008/1)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- dendritic cells, hyaluronic acid, LYVE-1, lymphatic endothelium, dermal dendritic cells, skin-draining lymph nodes, CD8+ T cell responses
- MeSH terms
- Animals, Cell Movement, Dendritic Cells, Endothelium, Lymphatic, Flow Cytometry, Glycoproteins, Humans, Hyaluronic Acid, Immunity, Cellular, Lymph Nodes, Mice, Transgenic, T-Lymphocytes, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Membrane Transport Proteins, Vesicular Transport Proteins, Lymphatic Vessels, Endothelial Cells, Mice
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