Drug Development, School of Medicine, Trinity College, Dublin, Ireland.
Analytical Sciences and Imaging, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Sci Rep. 2016 May 11;6:25520. doi: 10.1038/srep25520.
EBI2 is a G protein-coupled receptor activated by oxysterol 7α, 25-dihydroxycholesterol (7α25HC) and regulates T cell-dependant antibody response and B cell migration. We recently found EBI2 is expressed in human astrocytes, regulates intracellular signalling and modulates astrocyte migration. Here, we report that LPS treatment of mouse astrocytes alters mRNA levels of EBI2 and oxysterols suggesting that the EBI2 signalling pathway is sensitive to LPS-mediated immune challenge. We also find that conditioned media obtained from LPS-stimulated mouse astrocytes induces macrophage migration, which is inhibited by the EBI2 antagonist NIBR189. These results demonstrate a role for the EBI2 signalling pathway in astrocytes as a sensor for immune challenge and for communication with innate immune cells such as macrophages.
EBI2 是一种 G 蛋白偶联受体，可被氧化固醇 7α、25-二羟胆固醇（7α25HC）激活，调节 T 细胞依赖性抗体反应和 B 细胞迁移。我们最近发现 EBI2 在人星形胶质细胞中表达，调节细胞内信号转导并调节星形胶质细胞迁移。在这里，我们报告说 LPS 处理的小鼠星形胶质细胞改变了 EBI2 和氧化固醇的 mRNA 水平，表明 EBI2 信号通路对 LPS 介导的免疫挑战敏感。我们还发现，从 LPS 刺激的小鼠星形胶质细胞获得的条件培养基诱导巨噬细胞迁移，而 EBI2 拮抗剂 NIBR189 可抑制这种迁移。这些结果表明 EBI2 信号通路在星形胶质细胞中作为免疫挑战的传感器以及与先天免疫细胞（如巨噬细胞）进行通信的作用。
