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Endothelial Heparan Sulfate Controls Chemokine Presentation in Recruitment of Lymphocytes and Dendritic Cells to Lymph Nodes
Open accessAbstract
Heparan sulfate can bind several adhesion molecules involved in lymphocyte trafficking. However, the in vivo function of endothelial heparan sulfate in lymphocyte homing and stimulation of the immune response has not been elucidated. Here, we generated mutant mice deficient in the enzyme Ext1, which is required for heparan sulfate synthesis, in a Tek-dependent and inducible manner. Chemokine presentation was diminished in the mutant mice, causing the lack of appropriate integrin-mediated adhesion, and resulted in a marked decrease in lymphocyte sticking to high endothelial venules and in recruitment of resident dendritic cells through lymphatic vessels to the lymph nodes. As a consequence, mutant mice displayed a severe impairment in lymphocyte homing and a compromised contact hypersensitivity response. By contrast, lymphocyte rolling was increased because of loss of electrostatic repulsion by heparan sulfate. These results demonstrate critical roles of endothelial heparan sulfate in immune surveillance and immune response generation.
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“CCL21 has a positively charged C terminus that binds heparan sulfate and collagens in the interstitium and which, therefore, promotes haptotaxis (migration up a gradient of surface-bound chemoattractant) of DCs and T cells toward initial LVs (101, 102).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [101]
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Metadata
- Authors
- Bao, X., Moseman, E. A., Saito, H., Petryanik, B., Thiriot, A., Hatakeyama, S., Ito, Y., Kawashima, H., Yamaguchi, Y., Lowe, J. B., von Andrian, U. H., & Fukuda, M.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Harvard University (US)
- Case Western Reserve University (US)
- Corresponding author
- Fukuda, Minoru
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 33
- Issue
- 5
- Pages
- 817-829
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2996097
- OpenAlex
- W2037665285
- Cited by
- 167
- References
- 49
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 4 · 2019: 14 · 2018: 16 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 13 · 2013: 13 · 2012: 14
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-05-27)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (22659018, 21390023)
- National Cancer Institute (P01CA071932)
- National Institute of Allergy and Infectious Diseases (R01AI072252, R01AI069259)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- EXT1, lymphocyte homing, dendritic cell recruitment, lymph nodes, high endothelial venules, integrin-mediated adhesion, lymphatic vessels, contact hypersensitivity, immune surveillance, heparan sulfate synthesis
- MeSH terms
- Exostosin 1, Animals, Cell Adhesion, Dendritic Cells, Endothelium, Vascular, Heparan Sulfate, Lymph Nodes, Lymphocytes, Mice, Inbred C57BL, Venules, Integrins, N-Acetylglucosaminyltransferases, Chemokines, Mice
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