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

• Published in: Nature communications Vol. 14; no. 1; pp. 5837 - 23
• Main Authors: Mapunda, Josephine A., Pareja, Javier, Vladymyrov, Mykhailo, Bouillet, Elisa, Hélie, Pauline, Pleskač, Petr, Barcos, Sara, Andrae, Johanna, Vestweber, Dietmar, McDonald, Donald M., Betsholtz, Christer, Deutsch, Urban, Proulx, Steven T., Engelhardt, Britta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/28; 14/35; 14/69; 631/378/1341; 631/378/371; 631/378/87; 64/60; 82/1; Access control; Accessibility; Animals; Arachnoid; Arachnoid - diagnostic imaging; Brain; Cadherins; Central nervous system; Central Nervous System - diagnostic imaging; Cerebrospinal fluid; Compartments; E-cadherin; Female; Females; Humanities and Social Sciences; Imaging; Immune system; Immunosurveillance; Inflammation; Localization; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Meninges; Mice; Mice, Transgenic; multidisciplinary; Neuroimaging; Neuroinflammatory Diseases; Pia Mater; Science; Science (multidisciplinary); Spinal cord; Subarachnoid space; Surveillance; Transgenic mice
• ISSN: 2041-1723; 2041-1723
• 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. 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.