Highly dynamic dural sinus endothelial cells support meningeal immunity 4052

Description The CNS is covered by three interconnected membranes referred to as the meninges that host a diverse immune network. Situated within the skull-interfacing dura mater are venous sinuses, which are large veins thought to serve predominantly as passive blood drains for the brain and skull. Here, using intravital imaging, we revealed that the superior sagittal sinus and its associated endothelial cells are highly dynamic and constantly restructure to modulate fluid movement and immune surveillance. Specifically, we observed that the sagittal sinus is not a passive drain but instead constricts and dilates under smooth muscle control and Ramp1 signaling. In addition, the sinus wall is comprised of specialized endothelial cells that are highly fenestrated, allowing movement of fluids, macromolecules, and microbes between the sinus lumen and leukocyte-rich parasinus space. To protect this permeable interface, sinus endothelial cells (SECs) continually open and close their boundaries in a Ramp2 dependent manner. Transcranial Ramp2 antagonism impeded SEC boundary dynamics and immune cell movement along the sinus wall during steady state and after systemic viral infection. Interference with SEC dynamics during viral infection disrupted local antiviral immunity and facilitated pathogen entry into the meninges. These findings demonstrate that dural sinuses are dynamic venous drains with specialized SECs designed to support both steady state immune surveillance and antiviral immunity. Funding Sources This research was supported by the intramural program of the National Institute of Neurological Disorders and Stroke, NIH.