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神经退行性变中的神经炎症的解决:脉络丛中的白细胞募集。

The resolution of neuroinflammation in neurodegeneration: leukocyte recruitment via the choroid plexus.

机构信息

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

出版信息

EMBO J. 2014 Jan 7;33(1):7-22. doi: 10.1002/embj.201386609. Epub 2013 Dec 19.

Abstract

Inflammation is an integral part of the body's physiological repair mechanism, unless it remains unresolved and becomes pathological, as evident in the progressive nature of neurodegeneration. Based on studies from outside the central nervous system (CNS), it is now understood that the resolution of inflammation is an active process, which is dependent on well-orchestrated innate and adaptive immune responses. Due to the immunologically privileged status of the CNS, such resolution mechanism has been mostly ignored. Here, we discuss resolution of neuroinflammation as a process that depends on a network of immune cells operating in a tightly regulated sequence, involving the brain's choroid plexus (CP), a unique neuro-immunological interface, positioned to integrate signals it receives from the CNS parenchyma with signals coming from circulating immune cells, and to function as an on-alert gate for selective recruitment of inflammation-resolving leukocytes to the inflamed CNS parenchyma. Finally, we propose that functional dysregulation of the CP reflects a common underlying mechanism in the pathophysiology of neurodegenerative diseases, and can thus serve as a potential novel target for therapy.

摘要

炎症是身体生理修复机制的一个组成部分,除非它仍然没有得到解决并变得病理性,就像神经退行性变的渐进性质所表明的那样。基于来自中枢神经系统(CNS)以外的研究,现在人们明白,炎症的消退是一个主动的过程,它依赖于协调良好的先天和适应性免疫反应。由于中枢神经系统的免疫特权地位,这种消退机制在很大程度上被忽视了。在这里,我们讨论神经炎症的消退是一个依赖于一系列免疫细胞的网络的过程,这些细胞在一个严格调控的序列中运作,涉及大脑脉络丛(CP),这是一个独特的神经免疫界面,其位置是整合它从中枢神经系统实质接收的信号与来自循环免疫细胞的信号,并作为一个警报门,选择性地将炎症消退的白细胞募集到发炎的中枢神经系统实质中。最后,我们提出 CP 的功能失调反映了神经退行性疾病病理生理学中的一个共同潜在机制,因此可以作为治疗的一个潜在新靶点。

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