The Meningeal Lymphatic System and Brain Disease
WANG Jingbo, LI Jia*
The rediscovery of MLVs (meningeal lymphatic vessels) in 2015 changed the traditional view that “the central nervous system lacks a lymphatic system”. This article reviews the key findings in this field. Anatomically, murine MLVs can be divided into dorsal and ventral parts, which exhibit significant differences in lymphatic endothelial cell junction patterns, valve distribution, and CSF (cerebrospinal fluid) drainage efficiency. The zebrafish model has revealed the unique distribution and developmental dynamics of MLVs along the lateral and dorsal surfaces of the optic tectum and the cerebellum. Recent studies have shown that MLVs originate from venous endothelial cells and are precisely regulated by the PROX1, VEGFC-VEGFR3 signaling axis, and the Piezo1. VEGFC secreted by skull progenitor cells is essential for MLVs’ development. Functionally, MLVs drain CSF and cooperate with the glymphatic system to efficiently clear protein wastes such as amyloid-β, Tau protein, and α-synuclein. They also mediate central nervous system immune surveillance through antigen presentation and the transport of immune cells (dendritic cells and T cells). Regarding disease associations, aging induces MLVs degeneration via dural T cell accumulation and IFN-γ-mediated lymphatic endothelial injury, thereby exacerbating the pathological progression of Alzheimer’s disease and Parkinson’s disease. For brain tumors, MLVs-mediated antigen drainage benefits treatment, and modulating VEGFC signaling can enhance anti-tumor immunity and radiotherapy efficacy. In summary, research in the past decade has established the meningeal lymphatic system as a critical player in brain “waste clearance” and “immune surveillance”, offering new targets and translational directions for the diagnosis and treatment of neurodegenerative diseases, brain tumors, and agingrelated cognitive impairment.
CN
EN