IMMUNOLOGY2025™ Conference Recordings-Modulation of brain physiology and pathology by the meningeal lymphatic system

Modulation of brain physiology and pathology by the meningeal lymphatic system - Sandro da Mesquita

Video Transcription

Video Summary

The speaker describes Mayo Clinic research on the meningeal lymphatic system, focusing on how these vessels drain the brain, influence aging, and contribute to neurodegenerative and white matter diseases. The dura mater is presented as an immune-rich layer containing many immune cells and bona fide lymphatic vessels that drain cerebrospinal fluid and immune cells to cervical lymph nodes. <br /><br />The talk shows that these lymphatics are conserved in humans and mice, develop postnatally, and depend on VEGFC/VEGFR3 signaling. Using mouse models that impair lymphatic maintenance, the lab found that reduced lymphatic drainage leads to cognitive decline, altered immune cell trafficking, and worsened amyloid pathology in Alzheimer’s disease models. They also discovered that lymphatic dysfunction affects white matter: it lowers mature oligodendrocyte numbers, thins myelin, and disrupts remyelination. These effects appear to involve both innate and adaptive immune responses.<br /><br />The speaker then turns to leukodystrophies, especially CSF1R-related disease. In mouse models, impaired CSF1R signaling is linked to abnormal meningeal macrophages and reduced dura lymphatic vessels. Ongoing work suggests that depleting certain macrophages may allow lymphatic regrowth, potentially revealing new therapeutic targets for brain white matter disorders.

Keywords

meningeal lymphatic system

dura mater

cerebrospinal fluid drainage

neurodegenerative disease

Alzheimer’s disease

white matter disease

CSF1R-related disease