Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Nat Commun. 2023 Sep 20;14(1):5837. doi: 10.1038/s41467-023-41580-4.
Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1 cells located within the arachnoid beneath and separate from E-cadherin arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.
脑膜覆盖在大脑和脊髓表面，有助于保护和监测中枢神经系统（CNS）的免疫。然而，脑膜各层如何建立起具有不同免疫细胞和免疫介质可及性的 CNS 隔室尚不清楚。在这里，我们使用雌性转基因报告小鼠的双光子成像，描述了位于软脑膜和软膜细胞（形成软脑膜）的细胞间连接处的 VE-钙黏蛋白，以及充满脑脊液（CSF）的蛛网膜下腔（SAS）的边界。VE-钙黏蛋白的表达也标记了位于蛛网膜下腔下方的 Prox1 细胞层，与位于蛛网膜下腔的 E-钙黏蛋白蛛网膜屏障细胞分开。在雌性 VE-钙黏蛋白-GFP 报告小鼠的脊髓和大脑的体内成像中，我们可以直接观察到 CSF 衍生示踪剂和 T 细胞在健康和神经炎症期间进入由软膜和软膜边界的 SAS，以及在 CNS 病理期间检测到 SAS 体积的变化。总之，这些发现确定了 VE-钙黏蛋白是用于体内成像软脑膜的信息性标志物，可用于可视化 SAS 的边界，从而控制在健康和神经炎症期间免疫介质和免疫细胞进入 CNS 的能力。
