美国梅奥诊所Sandro Da Mesquita研究团队发现，脑膜淋巴功能促进少突胶质细胞的存活和大脑髓鞘化。相关论文于2024年8月31日在线发表在《免疫》杂志上。

研究人员发现，通过诱导成年小鼠的脑膜淋巴管去除，引起了神经胶质细胞的基因表达变化，随后成熟少突胶质细胞数量和特定脑部脂质种类减少。这些现象伴随着脑膜适应性免疫和脑髓样细胞激活的改变。在脑部再髓鞘化过程中，脑膜淋巴功能障碍引发了大脑中的免疫抑制状态，导致自发的少突胶质细胞补充延迟和轴突丢失。

免疫健全的小鼠中，因脑膜淋巴功能障碍而导致的成熟少突胶质细胞缺乏和神经炎症得到了完全的再现。被诊断为多发性硬化症的患者在脑脊液中呈现出血管内皮生长因子C的减少，尤其是在临床复发后不久，这可能表明脑膜淋巴功能不佳。这些数据表明，脑膜淋巴系统调节少突胶质细胞功能和大脑髓鞘化，这可能对人类脱髓鞘疾病具有重要意义。

据了解，脑膜淋巴功能障碍引起的具体神经生理变化尚不清楚。

附：英文原文

Title: Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination

Author: Sofia P. das Neves, Nickoleta Delivanoglou, Yingxue Ren, Chiara Starvaggi Cucuzza, Mateusz Makuch, Francisco Almeida, Guadalupe Sanchez, Megan J. Barber, Shanon Rego, Racquelle Schrader, Ayman H. Faroqi, Jean-Leon Thomas, Pamela J. McLean, Tiago Gil Oliveira, Sarosh R. Irani, Fredrik Piehl, Sandro Da Mesquita

Issue&Volume: 2024-08-31

Abstract: 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 in the brain 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.

DOI: 10.1016/j.immuni.2024.08.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00377-7