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- Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.
Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.
Citation | “Hyaluronan Synthesis Inhibition Impairs Antigen Presentation And Delays Transplantation Rejection.”. Matrix Biology : Journal Of The International Society For Matrix Biology, pp. 69-86. . |
Center | Stanford University |
Author | Payton L Marshall, Nadine Nagy, Gernot Kaber, Graham L Barlow, Amrit Ramesh, Bryan J Xie, Miles H Linde, Naomi L Haddock, Colin A Lester, Quynh-Lam Tran, Christiaan R de Vries, Aviv Hargil, Andrey Malkovskiy V, Irina Gurevich, Hunter A Martinez, Hedwich F Kuipers, Koshika Yadava, Xiangyue Zhang, Stephen P Evanko, John A Gebe, Xi Wang, Robert B Vernon, Carol de la Motte, Thomas N Wight, Edgar G Engleman, Sheri M Krams, Everett H Meyer, Paul L Bollyky |
Keywords | 4-methylumbelliferone, antigen presentation, Dendritic cells, Glycocalyx, Hyaluronan, transplantation |
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. |
Year of Publication |
2021
|
Journal |
Matrix biology : journal of the International Society for Matrix Biology
|
Volume |
96
|
Number of Pages |
69-86
|
Date Published |
12/2021
|
ISSN Number |
1569-1802
|
DOI |
10.1016/j.matbio.2020.12.001
|
Alternate Journal |
Matrix Biol
|
PMID |
33290836
|
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