VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation.

VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation.
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蛛网膜和PIA母细胞中的VE-钙粘着蛋白是CNS免疫监测和炎症体内成像的合适地标。

DOI:
10.1038/s41467-023-41580-4
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发表时间:
2023-09-20
影响因子:
16.6
通讯作者:
Engelhardt, Britta
Engelhardt, Britta
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mapunda, Josephine A.;Pareja, Javier;Vladymyrov, Mykhailo;Bouillet, Elisa;Helie, Pauline;Pleskac, Petr;Barcos, Sara;Andrae, Johanna;Vestweber, Dietmar;Mcdonald, Donald M.;Betsholtz, Christer;Deutsch, Urban;Proulx, Steven T.;Engelhardt, Britta

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脑膜覆盖大脑和脊髓的表面,并有助于保护和中枢神经系统(CNS)的免疫监视。然而,脑膜层如何建立对免疫细胞和免疫介质具有不同可及性的CNS隔室尚不清楚。在这里,使用双光子成像在雌性转基因报告小鼠,我们描述VE-钙粘蛋白在蛛网膜和软脑膜细胞,形成软脑膜和边界的蛛网膜下腔(SAS)充满脑脊液(CSF)的细胞间连接。VE-钙粘蛋白的表达也标志着一层Prox 1+细胞位于蛛网膜下方,并与E-钙粘蛋白+蛛网膜屏障细胞分开。在雌性VE-钙粘蛋白-GFP报告小鼠中的脊髓和脑的体内成像允许在健康和神经炎症期间直接观察CSF衍生的示踪剂和T细胞进入由蛛网膜和软脑膜界定的SAS的可及性,并检测CNS病理期间SAS的体积变化。总之,这些发现将VE-钙粘蛋白确定为软脑膜体内成像的信息标志,可用于可视化SAS的边界,从而显示软脑膜在健康和神经炎症期间控制免疫介质和免疫细胞进入CNS的潜在屏障特性。柔脑膜如何建立具有不同的免疫细胞和免疫介质可及性的CNS隔室仍然未知。在这里,作者显示了VE-钙粘蛋白在蛛网膜和软脑膜细胞中的连接定位,这使得体内软脑膜的潜在屏障特性可视化。
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. How the leptomeninges establish CNS compartments with different accessibility to immune cells and immune mediators remains unknown. Here, the authors show junctional localization of VE-cadherin in arachnoid and pia mater cells, which allows to visualize potential barrier properties of the leptomeninges in vivo.
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