Journal
NATURE NEUROSCIENCE
Volume 21, Issue 10, Pages 1380-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0227-9
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Funding
- National Institutes of Health [AG034113, NS096967, HL073402]
- National Multiple Sclerosis Society (NMSS)
- German Research Council (DFG) [CRC-TR-128, B11]
- Howard Hughes Medical Institute Medical Research Fellow Program
- Lymphatic Education & Research Network postdoctoral fellowship
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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.
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