Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination,Immunity

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Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination
Immunity ( IF 25.5 ) Pub Date : 2024-08-31 , DOI: 10.1016/j.immuni.2024.08.004
Sofia P das Neves ₁ , Nickoleta Delivanoglou ₁ , Yingxue Ren ₂ , Chiara Starvaggi Cucuzza ₃ , Mateusz Makuch ₄ , Francisco Almeida ₅ , Guadalupe Sanchez ₆ , Megan J Barber ₁ , Shanon Rego ₇ , Racquelle Schrader ₇ , Ayman H Faroqi ₆ , Jean-Leon Thomas ₈ , Pamela J McLean ₆ , Tiago Gil Oliveira ₉ , Sarosh R Irani ₁₀ , Fredrik Piehl ₃ , Sandro Da Mesquita ₆

Affiliation

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Centre for Neurology, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Neuroscience Ph.D. Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Post-baccalaureate Research Education Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Paris Brain Institute, Université Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Université, Paris Brain Institute, Paris, France.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal; Department of Neuroradiology, Hospital de Braga, 4710-243 Braga, Portugal.
Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK.

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.

中文翻译：

脑膜淋巴功能促进少突胶质细胞存活和脑髓鞘形成

脑膜淋巴功能障碍引起的确切神经生理学变化仍不清楚。在这里，我们表明，在成年小鼠中诱导脑膜淋巴管消融导致神经胶质细胞的基因表达发生变化，随后大脑中成熟少突胶质细胞数量和特定脂质种类减少。这些现象伴随着脑膜适应性免疫和脑髓细胞活化的改变。在脑髓鞘再生过程中，脑膜淋巴功能障碍引发免疫抑制状态，导致自发性少突胶质细胞补充延迟和轴突丢失。成熟少突胶质细胞的缺陷和由于脑膜淋巴功能受损引起的神经炎症仅在免疫功能正常的小鼠中进行了概括。诊断为多发性硬化症的患者表现为脑脊液中血管内皮生长因子 C 降低，尤其是在临床复发后不久，可能表明脑膜淋巴功能差。这些数据表明，脑膜淋巴调节少突胶质细胞功能和脑髓鞘形成，这可能对人类脱髓鞘疾病有影响。

更新日期：2024-08-31

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