Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB–dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-α in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

中文翻译：

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脱髓鞘后的促炎激活是髓磷脂清除和少突胶质细胞生成所必需的

髓鞘再生需要先天免疫系统功能，但小胶质细胞和巨噬细胞如何在损伤后清除髓鞘碎片并调整特定的再生反应尚不清楚。在这里，我们询问该过程是否需要促炎性小胶质细胞/巨噬细胞激活。我们在斑马鱼中建立了一种新的基于毒素的脊髓脱髓鞘和髓鞘再生模型，并表明吞噬细胞中促炎性 NF-κB 依赖性激活在髓磷脂损伤后迅速发生。我们发现促炎症反应依赖于骨髓分化初级反应88（MyD88）。MyD88 缺陷小鼠和斑马鱼不仅在髓磷脂碎片的降解方面受到损害，而且在启动用于髓磷脂修复的新少突胶质细胞的生成方面也受到损害。我们发现 MyD88 缺陷动物的病变中 TNF-α 的生成减少，TNF-α 是一种促炎分子，能够诱导新的髓鞘形成前少突胶质细胞的生成。我们的研究表明，促炎吞噬细胞信号是髓磷脂碎片降解、炎症消退和启动新少突胶质细胞生成所必需的。