Innate immunity triggers oligodendrocyte progenitor reactivity and confines damages to brain injuries
Innate immunity triggers oligodendrocyte progenitor reactivity and confines damages to brain injuries
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DOI：
10.1096/fj.05-5234fje
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Rivest, Serge
中科院分区：
文献类型：
--
作者：
Glezer, Isaias;Lapointe, Amelie;Rivest, Serge
先天性免疫反应被认为是一种损伤性反应，可以改善或恶化损伤后的大脑结果。因此，炎症分子可能会调节细胞易感性或愈合事件。脑损伤后的髓鞘再生依赖于少突胶质细胞祖细胞（OPC）的募集和控制分化和髓鞘产生的基因（如Olig1和Olig2 bHLH转录因子）的表达。我们的目标是确定先天免疫如何影响这些过程。在这里，我们报告，脂多糖（LPS）输液引发OPC反应。急性炎症改变了化学脱髓鞘后表达Olig1和Olig2的细胞的分布，增强了与髓鞘再生相关的转录信号的再现，并迅速清除了髓鞘碎片。尽管表达Olig1、Olig2和蛋白脂质蛋白的细胞在慢性炎症过程中被吸引到脱髓鞘位点，但髓鞘丢失与炎症对OPC反应性的影响无关。此外，脑免疫的有益特性被扩大到侵袭性损伤模型，其中LPS通过Toll样受体4（TLR4）减少表面活性剂介导的损伤，而抗炎治疗扩大了损伤。总之，小胶质细胞中的TLR4活化是在髓鞘再生水平改善修复和在具有强细胞溶解特性的试剂存在下保护脑组织的有力机制。
Regarded as a damaging reaction, innate immune response can either improve or worsen brain outcome after injury. Hence, inflammatory molecules might modulate cell susceptibility or healing events. The remyelination that follows brain lesions is dependent on the recruitment of oligodendrocyte progenitor cells (OPCs) and expression of genes controlling differentiation and myelin production, such as Olig1 and Olig2 bHLH transcription factors. We aimed to determine how innate immunity affects these processes. Here we report that lipopolysaccharide (LPS) infusion triggered OPC reactivity. Acute inflammation changed the distribution of Olig1- and Olig2-expressing cells following chemical demyelination, enhanced reappearance of transcription signals linked to remyelination and rapidly cleared myelin debris. Although cells expressing Olig1, Olig2, and proteolipid protein were attracted to demyelinated sites in the course of chronic inflammation, myelin loss was not associated with the effects of inflammation on OPC reactivity. In addition, the beneficial properties of brain immunity are broadened to an aggressive model of injury, wherein LPS through Toll-like receptor 4 (TLR4) reduced surfactant-mediated damage while anti-inflammatory treatment enlarged the lesion. In conclusion, TLR4 activation in microglia is a powerful mechanism for improving repair at the remyelination level and protecting the cerebral tissue in presence of agents with strong cytolytic properties.