ArticleMatrix biology : journal of the International Society for Matrix Biology2021
Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.
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Article in Matrix biology : journal of the International Society for Matrix Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
- Sliding into Place: The Lymphatic Vessel Endothelial Hyaluronan Receptor LYVE-1 and Its Role as a Mediator of Cell Entry and Trafficking in the Lymphatics.Biomolecules · 2026Review
- Label-Free Direct Detection of 4MU by Plasmon Enhanced Fluorescence Sensing Based on Ag@SiOJournal of fluorescence · 2025Article
- Surface-Engineered HA-PEG-ICG/PLGA Nanoprobes with Vessels Targeting for Lymphatic System Visualization.ACS applied bio materials · 2025Article
- Dual Effect of 4-Methylumbelliferone on INS1E Cells: Enhancing Migration and Glucose-Stimulated Insulin Secretion.International journal of molecular sciences · 2025Article
- Hyaluronan Accumulates in Inflamed Lymph Nodes and Promotes B-Cell Activation.Proteoglycan research · 2025Article
- Structure and unusual binding mechanism of the hyaluronan receptor LYVE-1 mediating leucocyte entry to lymphatics.Nature communications · 2025Article
- Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.Biomedicines · 2024Article
- Review
- Characterization of perivascular alveolar epithelial stem cells and their niche in lung homeostasis and cancer.Stem cell reports · 2024Article
- Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Virus-Derived Chemokine Modulating Protein Pre-Treatment Blocks Chemokine-Glycosaminoglycan Interactions and Significantly Reduces Transplant Immune Damage.Pathogens (Basel, Switzerland) · 2022Article
- Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System.Cells · 2021Review
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Authors and funding
28 authors at 4 institutions in 1 country.
Payton L MarshallDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Nadine NagyDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Gernot KaberDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Graham L BarlowDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Amrit RameshDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Bryan J XieDivision of Blood and Marrow Transplantation, Dept. of Medicine, Stanford University School of Medicine, CCSR, 1291 Welch Road, Stanford, CA 94305, United States.
Miles H LindeDivision of Hematology, Dept. of Medicine, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, SIM1, 265 Campus Drive, Stanford, CA 94305, United States.
Naomi L HaddockDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Colin A LesterDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Quynh-Lam TranDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Christiaan R de VriesDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Aviv HargilDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Andrey V MalkovskiyBiomaterials and Advanced Drug Delivery (BioADD) Laboratory Stanford School of Medicine, Stanford, CA 94304, United States.
Irina GurevichDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Hunter A MartinezDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Hedwich F KuipersDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Koshika YadavaDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States.
Xiangyue ZhangDepartment of Pathology, Stanford School of Medicine, 3373 Hillview Ave, Palo Alto CA 94304, United States.
Stephen P EvankoBenaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101, United States.
John A GebeBenaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101, United States.
Xi WangDivision of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford University School of Medicine, 1201 Welch Rd, MSLS P313, Stanford, CA 94305, United States.
Robert B VernonBenaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101, United States.
Carol de la MotteDepartment of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue Cleveland, OH 4419, United States.
Thomas N WightBenaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101, United States.
Edgar G EnglemanDivision of Hematology, Dept. of Medicine, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, SIM1, 265 Campus Drive, Stanford, CA 94305, United States.
Sheri M KramsDivision of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford University School of Medicine, 1201 Welch Rd, MSLS P313, Stanford, CA 94305, United States.
Everett H MeyerDivision of Blood and Marrow Transplantation, Dept. of Medicine, Stanford University School of Medicine, CCSR, 1291 Welch Road, Stanford, CA 94305, United States.
Paul L BollykyDivision of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, United States. Electronic address: pbollyky@stanford.edu.
Stanford University · USBenaroya Research InstituteStanford Medicine · USCleveland Clinic Lerner College of Medicine · US
Funding
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0MStanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI MANISHA DESAI · 2017 to 2026
$19.5MTissue Cytokine Sequestration and Immune Regulation in AutoimmunityU01AI101984 · NIAID · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2012 to 2021
$5.0MLymph Node Extracellular Matrix in Antigen Presentation and Immune RegulationR01DK096087 · NIDDK · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2012 to 2021
$3.4MThe Stanford Clinical Center for the Study of Type 1 Diabetes in Acute PancreatitisU01DK127395 · NIDDK · STANFORD UNIVERSITY · PI Marina Basina, Walter Gwang-Up Park · 2020 to 2026
$2.2MECM Costimulation of Immunoregulatory Pathways in Airway InflammationR01HL113294 · NHLBI · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2012 to 2016
$2.0MThe Role of Hyaluronan and CD44 in the Pathogenesis of Type 2 DiabetesR01DK116782 · NIDDK · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2020 to 2023
$1.6MThe Development of 4-methylumbelliferone Pro-drugs to Prevent Autoimmune DiabetesR01DK114174 · NIDDK · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2018 to 2020
$1.3MImmunization against Pf bacteriophage in Pseudomonas aeruginosa infectionK08AI151089 · NIAID · STANFORD UNIVERSITY · PI DE VRIES, CHRISTIAAN ROBERT · 2021 to 2021
$162kNHLBI NIH HHS R01 HL113294NIAID NIH HHS K08 AI151089NIAID NIH HHS T32 AI007290NIAID NIH HHS U01 AI101984NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK096087NIDDK NIH HHS R01 DK114174NIDDK NIH HHS R01 DK116782NIDDK NIH HHS U01 DK127395
Abstract
A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.
Indexed as
AnimalsAntigen PresentationCell ProliferationCells, CulturedDendritic CellsDisease Models, AnimalGraft RejectionHeart TransplantationHumansHyaluronic AcidHymecromoneLeukocytesMicePancreas TransplantationT-Lymphocytes, RegulatoryTransplantation, HomologousHyaluronic AcidHymecromone4-methylumbelliferoneAntigen presentationDendritic cellsGlycocalyxHyaluronanTransplantation
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