Production of low molecular weight polysialic acid and its anti-inflammatory effects on Siglec-11 expressing microglia and macrophages

中枢神经系统是α 2.8-连接聚唾液酸表达最高的器官。唾液酸结合免疫球蛋白样凝集素-11（Siglec-11）是识别α 2.8连接的唾液酸三聚体的小胶质细胞的人类谱系特异性抑制性受体。在这项研究中，我们将应用新型一次性袋技术来生产低分子量的人类相同的α 2.8连接的唾液酸。将检测可溶性α 2.8连接唾液酸与人Siglec-11的结合能力。此外，将在人诱导多能干（iPS）细胞衍生的小胶质细胞、人巨噬细胞以及小胶质细胞/巨噬细胞和人iPS细胞衍生的神经元的共培养物中分析可溶性α 2.8连接的唾液酸链对各种小胶质细胞和巨噬细胞功能（如细胞因子产生、吞噬作用、自由基产生和细胞活力）的影响。数据将阐明可溶性人类相同的α 2.8连接的唾液酸链作为靶向神经炎性疾病如多发性硬化症中的小胶质细胞和巨噬细胞的治疗性抗炎分子的适用性。

The central nervous system is the organ with highest expression of alpha2.8-linked polysialic acid. Sialic-acid-binding immunoglobulin-like lectin-11 (Siglec-11) is a human-lineage specific inhibitory receptor of microglia that recognizes alpha2.8-linked sialic acid trimers. In this study we will apply the novel disposable-bag technology to produce low molecular weight human-identical alpha2.8-linked sialic acids. The soluble alpha2.8-linked sialic acids will be tested in their binding capacity to human Siglec-11. Furthermore, effects of soluble alpha2.8-linked sialic acid chains on various microglia and macrophage functions such as cytokine production, phagocytosis, radical production and cell viability will be analyzed in human induced pluripotent stem (iPS) cell-derived microglia, human macrophages and co-cultures of microglia/macrophages and human iPS cell-derived neurons. Data will elucidate the suitability of soluble human-identical alpha2.8-linked sialic acid chains as therapeutic anti-inflammatory molecules targeting microglia and macrophages in neuroinflammatory diseases such as multiple sclerosis.