CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature

Antoine Louveau, Jasmin Herz, Maria Nordheim Alme, Andrea Francesca Salvador, Michael Q. Dong, Kenneth E. Viar, S. Grace Herod, James Knopp, Joshua C. Setliff, Alexander L. Lupi, Sandro Da Mesquita, Elizabeth L. Frost, Alban Gaultier, Tajie H. Harris, Rui Cao, Song Hu, John R. Lukens, Igor Smirnov, Christopher C. Overall, Guillermo OliverJonathan Kipnis

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1380-1391
Number of pages12
JournalNature neuroscience
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2018

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