RNA Sequencing of sorted CD31+ meningeal endothelial cells from naïve Lewis rats

The meninges, comprising the leptomeninges (pia and arachnoid layers) and the pachymeninx (dura layer), participate in CNS autoimmunity but their relative contributions remain unclear. Here, we report on findings in animal models of CNS autoimmunity and in multiple sclerosis patients, where, in chronic disease, the leptomeninges were highly inflamed and showed structural changes, while the dura mater was only marginally affected. Although dural vessels were leakier than leptomeningeal vessels, effector T cells adhered more weakly to the dural endothelium. Furthermore, local antigen presenting cells presented myelin and neuronal autoantigens less efficiently and the activation of autoreactive T cells was lower in dural than leptomeningeal layers, preventing local inflammatory processes. Direct antigen application was required to evoke a local inflammatory response in the dura. Together, our data demonstrate an uneven involvement of the meningeal layers in CNS autoimmunity, in which effector T cell trafficking and activation are functionally confined to the leptomeninges, while the dura remains largely shielded from CNS autoimmune processes.脑膜（meninges）由软脑膜蛛网膜层（leptomeninges，含软膜与蛛网膜两层结构）与硬脑膜层（pachymeninx，即硬脑膜）构成，其参与中枢神经系统（Central Nervous System，CNS）自身免疫过程，但各层膜的相对贡献迄今尚未明确。本研究针对中枢神经系统自身免疫性疾病动物模型与多发性硬化（multiple sclerosis）患者开展相关研究，结果显示：在慢性病程中，软脑膜蛛网膜层呈现显著炎症反应与结构改变，而硬脑膜仅受轻微影响。尽管硬脑膜血管的通透性高于软脑膜蛛网膜血管，但效应T细胞（effector T cells）与硬脑膜内皮细胞的黏附能力更弱。此外，硬脑膜区域的局部抗原呈递细胞（antigen presenting cells）呈递髓鞘（myelin）与神经元自身抗原的效率更低，自身反应性T细胞（autoreactive T cells）的活化水平也低于软脑膜蛛网膜层，由此抑制了局部炎症进程的发生。若要在硬脑膜区域诱导局部炎症反应，则需直接施加抗原刺激。综上，本研究数据证实，脑膜各层在中枢神经系统自身免疫中的参与程度并不均衡：效应T细胞的迁移与活化功能仅局限于软脑膜蛛网膜层，而硬脑膜在很大程度上免受中枢神经系统自身免疫过程的侵扰。