The meningeal lymphatic system is known to regulate neuroimmune functions, but how it affects resident brain cells is less clear. In a recent paper in Immunity, das Neves et al. partially ablated meningeal lymphatic vessels in mice by disrupting VEGF-C/D signaling. This resulted in a reduction in mature oligodendrocytes (MOLs) in the corpus callosum and motor cortex, along with disruption of brain lipid composition. Before the cells were lost, single-cell transcriptomics revealed altered gene expression, including of metabolic and oxidative stress genes, in MOLs. The effects of lymphatic vessel ablation on MOLs were not seen in mice that lacked CNS-associated mature T and B cells, or in mice with depleted CNS-associated innate immune cells. In addition, mice with ablated lymphatic vessels were slower than intact mice to recover from cuprizone-induced demyelination. Along these lines, the authors observed reduced VEGF-C levels in CSF samples from individuals with multiple sclerosis, suggesting that human demyelinating disease may involve impairments in meningeal lymphatic vasculature.

Original reference: Immunity https://doi.org/10.1016/j.immuni.2024.08.004 (2024)