CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Louveau A,Herz J,Alme MN,Salvador AF,Dong MQ,Viar KE,Herod SG,Knopp J,Setliff JC,Lupi AL,Da Mesquita S,Frost EL,Gaultier A,Harris TH,Cao R,Hu S,Lukens JR,Smirnov I,Overall CC,Oliver G,Kipnis J

doi

10.1038/s41593-018-0227-9

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1380-1391

issue

10

eissn

1097-6256

issn

1546-1726

pii

10.1038/s41593-018-0227-9

journal_volume

21

pub_type

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