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Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.

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

Author information

1
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA, USA. al2hk@virginia.edu.
2
Department of Neuroscience, University of Virginia, Charlottesville, VA, USA. al2hk@virginia.edu.
3
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA, USA.
4
Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
5
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
6
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
7
Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA.
8
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
9
Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
10
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA, USA. kipnis@virginia.edu.
11
Department of Neuroscience, University of Virginia, Charlottesville, VA, USA. kipnis@virginia.edu.
12
Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA. kipnis@virginia.edu.
13
Gutenberg Research Fellowship Group of Neuroimmunology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmnĀ²), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. kipnis@virginia.edu.

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.

PMID:
30224810
PMCID:
PMC6214619
[Available on 2019-03-17]
DOI:
10.1038/s41593-018-0227-9

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