CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.
Antoine LouveauJasmin HerzMaria Nordheim AlmeAndrea Francesca SalvadorMichael Q DongKenneth E ViarS Grace HerodJames KnoppJoshua C SetliffAlexander L LupiSandro Da MesquitaElizabeth L FrostAlban GaultierTajie H HarrisRui CaoSong HuJohn R LukensIgor SmirnovChristopher C OverallGuillermo OliverJonathan KipnisPublished in: Nature neuroscience (2018)
Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.
Keyphrases
- lymph node
- multiple sclerosis
- white matter
- inflammatory response
- blood brain barrier
- endothelial cells
- cerebrospinal fluid
- oxidative stress
- lipopolysaccharide induced
- gene expression
- resting state
- sentinel lymph node
- cerebral ischemia
- neoadjuvant chemotherapy
- randomized controlled trial
- public health
- ultrasound guided
- traumatic brain injury
- lps induced
- transcription factor
- functional connectivity
- dendritic cells
- immune response
- cell migration
- rectal cancer
- heat shock
- high glucose
- regulatory t cells
- heat shock protein