Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination

The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression that contributed to delayed spontaneous oligodendrocyte replenishment and axonal loss. The deficiencies in mature oligodendrocytes and neuroinflammation due to impaired meningeal lymphatic function were solely recapitulated in immunocompetent mice. Patients diagnosed with multiple sclerosis presented reduced vascular endothelial growth factor C in the cerebrospinal fluid, particularly shortly after clinical relapses, possibly indicative of poor meningeal lymphatic function. These data demonstrate that meningeal lymphatics regulate oligodendrocyte function and brain myelination, which might have implications for human demyelinating diseases. [Display omitted] •Meningeal lymphatic vessel ablation causes loss of mature oligodendrocytes•Demyelination due to meningeal lymphatic ablation relies on a competent immune system•Meningeal lymphatic dysfunction affects brain remyelination and aggravates axonal loss•Multiple sclerosis patients have decreased VEGF-C levels in their cerebrospinal fluid The neurophysiological processes regulated by meningeal lymphatic function remain unclear. das Neves et al. showed that meningeal lymphatic dysfunction leads to loss of mature oligodendrocytes and demyelination in the brain. Defective meningeal lymphatics incited a neuroinflammatory environment that limited oligodendrocyte replenishment after a demyelinating insult. This work might have therapeutic implications for the central nervous system demyelinating autoimmune disorders.