PD-1/PD-L1信号通路在脊髓损伤后巨噬/小胶质细胞极化过程中的作用研究

项目名称： PD-1/PD-L1信号通路在脊髓损伤后巨噬/小胶质细胞极化过程中的作用研究

项目编号： No.31271127

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 王键

作者单位： 中国人民解放军第四军医大学

项目金额： 85万元

中文摘要： 脊髓损伤后的炎症反应是脊髓损伤最为重要的病理过程之一，直接影响脊髓损伤的愈后。巨噬/小胶质细胞是脊髓损伤最主要的炎症细胞，它们可以极化为M1和M2型细胞，发挥不同的生理功能。PD-1/PD-L1信号通路是一条重要的共抑制性通路，它不仅调节淋巴细胞的活性，同时也调节巨噬细胞功能。我们前期研究显示：PD-1、PD-L1分子在脊髓损伤后表达水平逐渐增加；PD-1和PD-L1在巨噬/小胶质细胞表面均有表达；干预PD-1/PD-L1信号通路明显影响小鼠脊髓损伤后的运动功能恢复；PD-1-/-小鼠脊髓损伤后，M1型细胞数量增加，iNOS表达升高。这些结果说明：PD-1/PD-L1信号通路在脊髓损伤修复过程中具有重要作用。本课题采用PD-1-/-和TgPD-L1小鼠，通过体内和体外研究，详细阐明脊髓损伤后PD-1/PD-L1信号通路调节巨噬/小胶质细胞极化的分子机制，为今后脊髓损伤治疗提供新的理论基础。

中文关键词： PD-1；神经炎症；巨噬/小胶质细胞；极化；脊髓损伤

英文摘要： The inflammatory response is one of the most important pathological processes to influence prognosis directly after spinal cord injury. The main inflammatory cells are infiltrated macrophages and residential activated microglia after spinal cord injury (SCI). Both of them can be polarized to M1 or M2 microphage based on environment they are located at to give different physiological functions. PD-1/PD-L1 pathway is a critical co-inhibitory signaling to regulate not only activity of lymphocytes, but also the function of macrophages. Our preliminary data showed that the transcripts of PD-1 and PD-L1 were gradually increased after SCI. PD-L1 as well as PD-1 expressed on macrophages/microglia which located at lesion site. The motor function was promoting to recovery with spinal cord crushing in TgPD-L1 mice. On the contrary, PD-1-/- mice became worse in their recovery of motor function after SCI. The M1 macrophages were obviously increased in PD-1-/- mice compared with wild type mice after SCI. And the iNOS, the specific marker of M1 macrophages was upregulated. These results showed that the PD-1/PD-L1 pathway played critical roles in macrophages/microglia polarization after SCI. It might influence the prognosis of injured spinal cord by regulating the polarization of macrophages/microglia after SCI. In this study,

英文关键词： PD-1；neuroinflammation；macrophage/microglia；polarization；spinal cord injury