ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Role of high endothelial venule-expressed heparan sulfate in chemokine presentation and lymphocyte homing.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting high endothelial venules: potential strategies for cancer treatment.Annals of medicine · 2025Review
- Tumour-associated vasculature in T cell homing and immunity: opportunities for cancer therapy.Nature reviews. Immunology · 2025Review
- Pipelines for lymphocyte homeostasis maintenance during cancer immunotherapy.Frontiers in immunology · 2025Review
- Chemokine positioning determines mutually exclusive roles for their receptors in extravasation of pathogenic human T cells.bioRxiv : the preprint server for biology · 2023Article
- CHST4 might promote the malignancy of cholangiocarcinoma.PloS one · 2022Article
- High endothelial venules (HEVs) in immunity, inflammation and cancer.Angiogenesis · 2021Review
- Article
- Contribution of Heparan Sulphate Binding in CCL21-Mediated Migration of Breast Cancer Cells.Cancers · 2021Article
- High Endothelial Venules: A Vascular Perspective on Tertiary Lymphoid Structures in Cancer.Frontiers in immunology · 2021Review
- Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors.Frontiers in oncology · 2020Article
- Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer.Journal of leukocyte biology · 2018Review
- Advances in the pathogenesis and possible treatments for multiple hereditary exostoses from the 2016 international MHE conference.Connective tissue research · 2018Article
- Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Biosynthesis and Functional Significance of Peripheral Node Addressin in Cancer-Associated TLO.Frontiers in immunology · 2016Review
- Vascular endothelial growth factor c/vascular endothelial growth factor receptor 3 signaling regulates chemokine gradients and lymphocyte migration from tissues to lymphatics.Transplantation · 2015Article
- Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects.PloS one · 2014Article
- Human genetic disorders and knockout mice deficient in glycosaminoglycan.BioMed research international · 2014Review
- Heparan sulfate: a ubiquitous glycosaminoglycan with multiple roles in immunity.Frontiers in immunology · 2013Article
- Heparan sulfate is essential for thymus growth.The Journal of biological chemistryArticle
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Lymphocyte homing to peripheral lymph nodes (PLNs) is mediated by multistep interactions between lymphocytes and high endothelial venules (HEVs). Heparan sulfate (HS) has been implicated in the presentation of chemokines on the surface of HEVs during this process. However, it remains unclear whether this cell surface presentation is a prerequisite for lymphocyte homing. In this study, we generated conditional knockout (cKO) mice lacking Ext1, which encodes a glycosyltransferase essential for HS synthesis, by crossing Ext1(flox/flox) mice with GlcNAc6ST-2-Cre transgenic mice expressing Cre recombinase in HEVs. Immunohistochemical studies indicated that HS expression was specifically eliminated in PLN HEVs but retained in other blood vessels in the cKO mice. The accumulation of a major secondary lymphoid tissue chemokine, CCL21, on HEVs was also abrogated without affecting CCL21 mRNA levels, indicating that HS presents CCL21 on HEVs in vivo. Notably, a short-term lymphocyte homing assay indicated that lymphocyte homing to PLNs was diminished in the cKO mice by 30-40%. Consistent with this result, contact hypersensitivity responses were also diminished in the cKO mice. The residual lymphocyte homing to PLNs in the cKO mice was dependent on pertussis toxin-sensitive Gi protein signaling, in which lysophosphatidic acid-mediated signaling was partly involved. These results suggest that chemokine presentation by HS on the surface of HEVs facilitates but is not absolutely required for lymphocyte homing.
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Registered trials
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