Dectin-1受体调节小胶质细胞促进少突胶质前体细胞分化介导髓鞘再生的机制研究

在脱髓鞘病理条件下，小胶质细胞极化成M1或M2型分别参与髓鞘的损伤或修复的调控。M2型小胶质细胞能够促进少突胶质前体细胞的分化，促进髓鞘的再生。全基因组基因表达分析发现了小胶质细胞中的Dectin-1基因上调有助于髓鞘的再生修复，但其生物学机制尚不清楚。本项目拟研究Dectin-1受体调节小胶质细胞促进少突胶质前体细胞分化进行髓鞘再生的分子机制。首先，在野生型和Dectin-1基因敲除小鼠中建立脱髓鞘疾病模型，确证Dectin-1受体在髓鞘再生修复中发挥着重要调节作用。并深入研究Dectin-1受体是否调节小胶质细胞从M1转变成M2型，及对炎症/抗炎细胞因子、神经营养因子及活化素A表达变化的影响；及Dectin-1对少突胶质前体细胞或少突胶质细胞的形成及分布的影响。项目拟揭示Dectin-1受体调节小胶质细胞促进少突胶质前体细胞进行髓鞘再生修复的分子机制，为药物靶点的筛选提供重要的基础。

In the pathological condition of demyelination，the polarization of microglia into M1 or M2 are involved in the regulation of demyelination or remyelination, respectively. Microglia in M2 status promotes the differentiation of oligodendrocyte precursor cells, and then regulates remyelination. Genome-wide gene expression analysis revealed that upregulation of Dectin-1 gene in microglial cells contributes to the remyelination, but its biological mechanism remains unclear. This project intends to study the molecular mechanisms by which Dectin-1 receptor regulates microglia to promote the differentiation of oligodendrocyte progenitor cells for remyelination. First of all, we would establish a model of demyelinating disease in wild mice and Dectin-1 knockout mice to confirm that Dectin-1 receptor is a molecule that plays an important regulatory role in remyelination. Next, we would study whether Dectin-1 receptor regulates microglia shifting from the M1 status to the M2 status, causing expression changes of inflammatory/anti-inflammatory cytokines, neurotrophic factor, and activin-A, as well as the effect of Dectin-1 on the formation and distribution of oligodendrocyte progenitor cells or oligodendrocytes. The project intends to reveal the molecular mechanism of Dectin-1 receptor in regulating microglia to promote oligodendrocyte precursor cells for remyelination, and provide molecular basis for screening novel drug targets.