전한울
2024년 10월 8일
- Meningeal lymphatic 기능 저하: mouse의 lymphatics를 절제하여 림프 배출을 차단하면 mature oligodendrocyte가 감소하고 특정 지질 성분이 감소하는 등 뇌의 생리학적 변화가 발생함.
뇌의 remyelination 지연: Meningeal lymphatics 기능 저하는 remyelination을 지연시키고, axon 손실을 유도함.
다발성 경화증과의 연관성: 다발성 경화증 환자의 뇌척수액에서 VEGF-C 수준이 감소한 것이 관찰되었으며, 이는 수막 림프 기능의 저하와 관련이 있을것으로 보임
결과: 뇌의 탈수초성 자가면역 질환 치료에 있어 Meningeal lymphatic기능을 개선하는 접근이 도움이 될 수 있을것임.
https://doi.org/10.1016/j.immuni.2024.08.004
Summary
The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression that contributed to delayed spontaneous oligodendrocyte replenishment and axonal loss. The deficiencies in mature oligodendrocytes and neuroinflammation due to impaired meningeal lymphatic function were solely recapitulated in immunocompetent mice. Patients diagnosed with multiple sclerosis presented reduced vascular endothelial growth factor C in the cerebrospinal fluid, particularly shortly after clinical relapses, possibly indicative of poor meningeal lymphatic function. These data demonstrate that meningeal lymphatics regulate oligodendrocyte function and brain myelination, which might have implications for human demyelinating diseases.
