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alpha2.8-linked poly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）是一种人类谱系特异性小胶质细胞抑制受体，可识别α 2.8链唾液酸三聚体。在这项研究中，我们将应用新的一次性袋技术来生产低分子量的人类相同的alpha2.8链唾液酸。可溶性α 2.8链唾液酸将测试其与人类siglece -11的结合能力。此外，在人诱导多能干细胞（iPS）衍生的小胶质细胞、人巨噬细胞以及小胶质/巨噬细胞和人iPS细胞衍生的神经元共培养中，将分析可溶性α 2.8连接唾液酸链对各种小胶质细胞和巨噬细胞功能的影响，如细胞因子的产生、吞噬、自由基的产生和细胞活力。数据将阐明可溶性人同α 2.8链唾液酸链作为治疗性抗炎分子靶向小胶质细胞和巨噬细胞治疗多发性硬化症等神经炎性疾病的适用性。

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.