Unraveling the lymphatic system in the spinal cord meninges: a critical element in protecting the central nervous system

The lymphatic vasculature plays a crucial role in fluid clearance and immune responses in peripheral organs by connecting them to distal lymph nodes. Recently, attention has been drawn to the lymphatic vessel network surrounding the brain’s border tissue (Aspelund et al. in J Exp Med 212:991–999, 2015. https://doi.org/10.1084/jem.20142290 ; Louveau et al. in Nat Neurosci 21:1380–1391, 2018. https://doi.org/10.1038/s41593-018-0227-9 ), which guides immune cells in mediating protection against tumors (Song et al. in Nature 577:689–694, 2020. https://doi.org/10.1038/s41586-019-1912-x ) and pathogens Li et al. (Nat Neurosci 25:577–587, 2022. https://doi.org/10.1038/s41593-022-01063-z ) while also contributing to autoimmunity (Louveau et al. 2018) and neurodegeneration (Da Mesquita et al. in Nature 560:185–191, 2018. https://doi.org/10.1038/s41586-018-0368-8 ). New studies have highlighted the integral involvement of meningeal lymphatic vessels in neuropathology. However, our limited understanding of spinal cord meningeal lymphatics and immunity hinders efforts to protect and heal the spinal cord from infections, injury, and other immune-mediated diseases. This review aims to provide a comprehensive overview of the state of spinal cord meningeal immunity, highlighting its unique immunologically relevant anatomy, discussing immune cells and lymphatic vasculature, and exploring the potential impact of injuries and inflammatory disorders on this intricate environment.