Aberrant oligodendroglial-vascular interactions disrupt the Blood Brain Barrier triggering CNS inflammation

Disruption of the blood brain barrier (BBB) is critical to initiation and perpetuation of disease in Multiple Sclerosis (MS). We report here an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent remyelination. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in active MS lesions, representing an inability to properly detach from vessels following perivascular migration. These perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte end feet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates this dysfunctional vascular detachment, and also leads to OPC secretion of Wif1, that interferes with Wnt ligand function on endothelial cell tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that it may be both an impediment t...

血脑屏障（blood brain barrier, BBB）的破坏是多发性硬化（Multiple Sclerosis, MS）发生与持续进展的核心环节。本研究报道了多发性硬化中少突胶质细胞与脉管系统之间的相互作用，该相互作用可区分人类白质损伤与正常啮齿类动物髓鞘再生的不同特征。我们在活动性MS病灶中观察到少突胶质前体细胞（oligodendrocyte precursor cells, OPCs）的血管周围簇集现象，这表明这些细胞在完成血管周围迁移后无法正常脱离血管管壁。这些位于血管周围的OPCs本身可破坏BBB，通过干扰星形胶质细胞终足与内皮细胞紧密连接的完整性，引发血管通透性改变及相关中枢神经系统炎症。少突胶质前体细胞内异常的Wnt信号张力介导了这种功能异常的血管脱离过程，同时还可促使OPCs分泌Wif1，后者可通过干扰Wnt配体对内皮细胞紧密连接完整性的调控作用产生负面影响。多发性硬化中这种存在缺陷的少突胶质细胞-脉管系统相互作用的相关证据表明，其或可既是一种阻碍