CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature [2D2 T cells]. Mus musculus

Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention. Overall design: Adult C57Bl6 mice were injected with 2D2 tdTOMATO T cells prior to meningeal lymphatic ablation (VIS) or control (PBS). EAE was induced with MOG(35-55). Activated 2D2 T cells (TCRb+CD4+CD44+tdTOMATO+) were isolated from dCLN and spleen at day8 post EAE induction