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Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN

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Mitchell, Daniel A., Zhang, Qiang , Voorhaar, Lenny, Haddleton, David M., Herath, Shan, Gleinich, Anne S., Randeva, Harpal S., Crispin, Max, Lehnert, Hendrik, Wallis, Russell, Patterson, Steven and Becer, C. Remzi (2017) Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN. Chemical Science, 8 (10). pp. 6974-6980. doi:10.1039/c7sc01515a

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Official URL: http://doi.org/10.1039/C7SC01515A

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Abstract

The human C-type lectin DC-SIGN (CD209) is a significant receptor on the surface of dendritic cells (DCs) – crucial components of host defense that bridge the innate and adaptive immune systems. A range of linear glycopolymers, constructed via controlled radical polymerization techniques have been shown to interact with DC-SIGN with affinities in the physiologically active range. However, these first generation glycopolymers possess limited structural definition and their effects on DCs were not known. Here we report the development of star-shaped mannose glycopolymers with the aim of targeting the clustered domain arrangement of DC-SIGN and these were shown to bind with picomolar affinity. Increased secretion of IL-10 with simultaneous decrease in secreted IL-12p70 occurred in activated DCs incubated with star-shaped glycopolymers – a cytokine secretion pattern characteristic of wound-healing tissue environments. Incorporating stellar architecture into glycopolymer design could be key to developing selective and very high-affinity therapeutic materials with distinct immunomodulatory and tissue repair potential.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science > Chemistry
Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit
Faculty of Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Dendritic cells, Cytokines
Journal or Publication Title: Chemical Science
Publisher: Royal Society of Chemistry
ISSN: 2041-6520
Official Date: 16 August 2017
Dates:
DateEvent
16 August 2017Available
11 August 2017Accepted
Volume: 8
Number: 10
Page Range: pp. 6974-6980
DOI: 10.1039/c7sc01515a
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
EuroSequences Proposal No: 642083 European Commissionhttp://dx.doi.org/10.13039/501100000780
EP/P009018/1Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
UNSPECIFIEDCoventry General Charities UKUNSPECIFIED
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