Visualizing the Role of Myeloid Cells During CNS Autoimmunity

可视化骨髓细胞在中枢神经系统自身免疫过程中的作用

• 批准号: 165173437
• 负责人: Professor Dr. Alexander Flügel
• 金额: --
• 依托单位: Abteilung Neuroimmunologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/165173437?language=en
• 关键词: Visualizing; Role; Myeloid; Cells; During

In this project we will study the function of myeloid cells during the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The following questions will be followed: 1. What are the migratory steps of myeloid cells into the CNS during incipient EAE? 2. What are the molecular cues that mediate their transmigration of the blood brain barrier (BBB)? 3. What role do myeloid cells play in opening the BBB? 4. Which myeloid cells mediate the initial antigen presentation to autoaggressive encephalitogenic T cells? The methodic focus of this project lies in the combination of 2-photon laser scanning microscopy with functional/molecular analyses. Myeloid cells will be made visible by staining them with fluorescence dyes or by use of genetically encoded fluorescence proteins. The migratory behavior of the cells at the BBB and in the different CNS milieus and EAE phases will be visualized by live 2-PM. The analyses of the interactions of myeloid cells with autoagressive T cells in acute and chronic EAE models will be performed using functional markers which will be introduced into the T cells. These markers will make possible the visualization of the binding between T cells and myeloid APCs and the consecutive activation of the effector T cells.

在这个项目中，我们将研究髓系细胞在实验性自身免疫性脑脊髓炎(EAE)启动过程中的功能，EAE是多发性硬化症的动物模型。以下问题将被提出：1.在早期EAE中，髓系细胞向中枢神经系统迁移的步骤是什么？2.是什么分子信号调节它们迁移到血脑屏障(BBB)？3.髓系细胞在打开血脑屏障中起什么作用？4.哪些髓系细胞介导了最初的抗原递呈给自身侵袭性脑T细胞？该项目的方法学重点在于将双光子激光扫描显微镜与功能/分子分析相结合。通过用荧光染料染色或使用基因编码的荧光蛋白，髓系细胞将变得可见。细胞在血脑屏障和不同的中枢神经系统环境和EAE时相的迁移行为将通过实时2-PM可视化。分析急性和慢性EAE模型中髓系细胞和自进性T细胞的相互作用将使用将被引入T细胞的功能标记物。这些标记物将使可视化T细胞与髓系APC之间的结合以及效应器T细胞的连续激活成为可能。