Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN.
Manipulation of cytokine secretion in human dendritic cells using glycopolymers with picomolar affinity for DC-SIGN.
复制标题
DOI：
10.1039/c7sc01515a
复制
发表时间：
2017-10-01
期刊：
影响因子：
8.4
通讯作者：
Becer CR
中科院分区：
文献类型：
--
作者：
Mitchell DA;Zhang Q;Voorhaar L;Haddleton DM;Herath S;Gleinich AS;Randeva HS;Crispin M;Lehnert H;Wallis R;Patterson S;Becer CR
树突状细胞是连接先天免疫系统和适应性免疫系统的桥梁，它们可以被星星状的糖聚合物操纵。人C型凝集素DC-SIGN（CD 209）是树突状细胞（DC）表面上的重要受体，树突状细胞是连接先天性免疫系统和适应性免疫系统的宿主防御的关键组分。通过受控自由基聚合技术构建的一系列线性糖基共聚物已被证明与DC-SIGN相互作用，其亲和力在生理活性范围内。然而，这些第一代糖聚合物具有有限的结构定义，并且它们对DC的影响尚不清楚。在这里，我们报告了星形甘露糖糖聚合物的发展，其目的是靶向DC-SIGN的聚集结构域排列，并且这些显示出以皮摩尔亲和力结合。在与星形糖聚合物孵育的活化DC中，IL-10分泌增加，同时分泌的IL-12 p70减少-这是伤口愈合组织环境的细胞因子分泌模式特征。将星形结构转化为糖基共聚物设计可能是开发具有独特免疫调节和组织修复潜力的选择性和非常高亲和力的治疗材料的关键。
Dendritic cells bridge the innate and adaptive immune systems and they can be manipulated by star shaped glycopolymers. 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.
登录
查看更多内容
影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
15
作者：
Becer, C. Remzi;Gibson, Matthew I.;Geng, Jin;Ilyas, Rebecca;Wallis, Russell;Mitchell, Daniel A.;Haddleton, David M.
通讯作者：
Haddleton, David M.
影响因子：
2.9
作者：
Pederson K;Mitchell DA;Prestegard JH
通讯作者：
Prestegard JH
影响因子：
5.4
作者：
Martin, MP;Lederman, MM;Carrington, M
通讯作者：
Carrington, M
影响因子：
16.6
作者：
Zhang, Qiang;Collins, Jennifer;Haddleton, David M.
通讯作者：
Haddleton, David M.