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.

中文翻译：

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使用对DC-SIGN具有皮摩尔亲和力的糖聚合物操纵人树突状细胞中细胞因子的分泌

人类C型凝集素DC-SIGN（CD209）是树突状细胞（DCs）表面上的重要受体，树突状细胞是宿主防御的重要组成部分，可桥接先天性和适应性免疫系统。一系列直链糖聚合物，通过已证明受控的自由基聚合技术可在生理活性范围内与DC-SIGN相互作用。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的作用是未知的。在这里，我们报道了星形甘露糖糖多聚体的发展，其目标是靶向DC-SIGN的簇结构域排列，并显示它们与皮摩尔亲和力结合。在与星形糖聚合物孵育的活化DC中，IL-10的分泌增加，而分泌的IL-12p70却同时减少，这是伤口愈合组织环境特有的细胞因子分泌模式。