Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
Antoine Louveau, … , Maiken Nedergaard, Jonathan Kipnis
Antoine Louveau, … , Maiken Nedergaard, Jonathan Kipnis
Published September 1, 2017
Citation Information: J Clin Invest. 2017;127(9):3210-3219. https://doi.org/10.1172/JCI90603.
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Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

Abstract

Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.

Authors

Antoine Louveau, Benjamin A. Plog, Salli Antila, Kari Alitalo, Maiken Nedergaard, Jonathan Kipnis

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Figure 3

Potential modulation of T cell activation by lymphatic ECs.

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Potential modulation of T cell activation by lymphatic ECs. Lymphatic EC...
Lymphatic ECs (LECs) (primarily within the lymph nodes) can modulate T cell activation directly, either by producing modulatory molecules (NO, IDO, TGF-β) or by expressing MHC and costimulatory molecules like PDL1. Alternatively, the regulation can also be indirect by inducing maturation of dendritic cells (DCs) via ICAM-1 expression. Moreover, soluble molecules draining from the CSF to the dcLNs are taken up by subcapsular APCs (DCs and macrophages), resulting in modulation of B and T cell activation in the dcLNs. This function of meningeal lymphatic vessels in regulation of meningeal T cell tolerance has not yet been explored. IDO, Indoleamine 2,3-dioxygenase; PD1, programmed death 1; PDL1, Programmed death ligand 1.