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Acta Neuropathol. 2019 Nov 6. doi: 10.1007/s00401-019-02091-z. [Epub ahead of print]

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges.

Author information

1
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK.
2
Department of Anaesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
3
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA.
4
The Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK.
5
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
6
UCL Institute of Ophthalmology, University College London, London, UK.
7
Clinical Neurosciences (Neuropathology), Faculty of Medicine, Southampton University Hospitals, Southampton, SO16 6YD, UK.
8
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
9
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK. j.rihel@ucl.ac.uk.

Abstract

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

KEYWORDS:

CNS lymphatics; CNS macrophages; Lymphatics; Macrophages; Meningeal lymphatics

PMID:
31696318
DOI:
10.1007/s00401-019-02091-z

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