title: Structural and functional features of central nervous system lymphatic vessels.
abstract: One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Antoine
authors.initials: A
authors.lastname: Louveau
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Smirnov
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Keyes
authors.affiliation: 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Medicine (Division of Allergy), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Eccles
authors.affiliation: 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Sherin J
authors.initials: SJ
authors.lastname: Rouhani
authors.affiliation: 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Peske
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Noel C
authors.initials: NC
authors.lastname: Derecki
authors.affiliation: Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: David
authors.initials: D
authors.lastname: Castle
authors.affiliation: Department of Pathology (Neuropathology), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Mandell
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Tajie H
authors.initials: TH
authors.lastname: Harris
authors.affiliation: 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kipnis
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000033:anatomy & histology* / Q000166:cytology / Q000276:immunology*; D003392:Cranial Sinuses / Q000033:anatomy & histology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology; D042601:Lymphatic Vessels / Q000033:anatomy & histology* / Q000166:cytology / Q000276:immunology*; D008297:Male; D008578:Meninges / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology