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

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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.