Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN.pdf (1.12 MB)
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Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN.

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journal contribution
posted on 30.04.2018, 10:37 by Daniel A. Mitchell, Qiang Zhang, Lenny Voorhaar, David M. Haddleton, Shan Herath, Anne S. Gleinich, Harpal S. Randeva, Max Crispin, Hendrik Lehnert, Russel Wallis, Steven Patterson, C. Remz Becer
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.

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Citation

Chemical Science, 2017, 8, pp. 6974-6980

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Chemical Science

Publisher

Royal Society of Chemistry

issn

2041-6520

eissn

2041-6539

Acceptance date

11/08/2017

Copyright date

2017

Available date

30/04/2018

Publisher version

http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC01515A#!divAbstract

Language

en

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