The meninges: new therapeutic targets for multiple sclerosis.
The meninges: new therapeutic targets for multiple sclerosis.
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DOI：
10.1016/j.trsl.2014.08.005
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Brown MA
中科院分区：
文献类型：
--
作者：
Russi AE;Brown MA
CNS主要由非再生细胞组成，包括神经元和产生髓鞘的少突胶质细胞，它们特别容易受到免疫细胞介导的损伤。为了保护CNS，存在通常限制外周免疫细胞转运到脑和脊髓中的机制，赋予“免疫特化”状态。因此，关于在包括多发性硬化（MS）在内的几种CNS炎性疾病中如何克服这些限制一直存在长期争论。在这篇综述中，我们强调了脑膜的作用，脑膜是围绕和保护中枢神经系统和封闭脑脊液的组织，在促进慢性炎症导致神经元损伤。虽然脑膜传统上被认为是为大脑和脊髓提供物理保护的结构，但新的数据已经确定这些组织是主动免疫的部位。据推测，脑膜是中枢神经系统正常免疫监视的重要参与者，但也是抗髓鞘免疫应答的起始部位。由此产生的强烈脑膜炎症导致局部血液屏障完整性丧失，并促进免疫细胞大规模流入CNS实质。我们认为，靶向介导脑膜内这些炎症反应的细胞和分子为MS提供了有希望的治疗方法，这些治疗方法不受血脑屏障的限制。重要的是，这种疗法可以避免通常与现有治疗相关的全身性免疫抑制。
The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments.
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