Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.
Animals
Antigen Presentation
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Dendritic Cells
/ cytology
Disease Models, Animal
Graft Rejection
/ immunology
Heart Transplantation
/ adverse effects
Humans
Hyaluronic Acid
/ biosynthesis
Hymecromone
/ administration & dosage
Leukocytes
/ cytology
Mice
Pancreas Transplantation
/ adverse effects
T-Lymphocytes, Regulatory
/ cytology
Transplantation, Homologous
4-methylumbelliferone
Antigen presentation
Dendritic cells
Glycocalyx
Hyaluronan
Transplantation
Journal
Matrix biology : journal of the International Society for Matrix Biology
ISSN: 1569-1802
Titre abrégé: Matrix Biol
Pays: Netherlands
ID NLM: 9432592
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
08
2020
revised:
03
12
2020
accepted:
03
12
2020
pubmed:
9
12
2020
medline:
3
11
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33290836
pii: S0945-053X(20)30116-5
doi: 10.1016/j.matbio.2020.12.001
pmc: PMC8147171
mid: NIHMS1657174
pii:
doi:
Substances chimiques
Hymecromone
3T5NG4Q468
Hyaluronic Acid
9004-61-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-86Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK114174
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116782
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI151089
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK116074
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK096087
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007290
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113294
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI101984
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no competing financial interests. N.N., P.L.M., and P.L.B. are listed as inventors of the patent (PCT/US2019/019310) filed by the Board of Trustees of the Leland Stanford Junior University.
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