Abstract：
Macrophage recruitment to the injured nerve initiates a cascade of events, including myelin debris clearance and nerve trophic factor secretion, which contribute to proper nerve tissue repair. However, the mechanism of macrophage recruitment is still unclear. Here, by comparing wild-type with Mlkl-/- and Sarm1-/- mice, two mouse strains with impaired myelin debris clearance after peripheral nerve injury, we identify interleukin-17B (IL-17B) as a key regulator of macrophage recruitment. Schwann-cell-secreted IL-17B acts in an autocrine manner and binds to IL-17 receptor B to promote macrophage recruitment, and global or Schwann-cell-specific IL-17B deletion reduces macrophage infiltration, myelin clearance, and axon regeneration. We also show that the IL-17B signaling pathway is defective in the injured central nerves. These results reveal an important role for Schwann cell autocrine signaling during Wallerian degeneration and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.
摘要：
巨噬细胞募集到受伤的神经会引发一系列事件，包括髓鞘碎片清除和神经营养因子分泌，有助于适当的神经组织修复。然而,巨噬细胞募集的机制尚不清楚。这里,通过比较野生型与Mlkl-/-和Sarm1-/-小鼠，周围神经损伤后髓磷脂碎片清除受损的两种小鼠品系，我们确定白细胞介素-17B(IL-17B)是巨噬细胞募集的关键调节因子.雪旺细胞分泌的IL-17B以自分泌方式起作用，并与IL-17受体B结合以促进巨噬细胞募集，和全局或雪旺氏细胞特异性IL-17B缺失减少巨噬细胞浸润，髓鞘清除,和轴突再生。我们还表明，IL-17B信号通路在受损的中枢神经中存在缺陷。这些结果揭示了沃勒变性过程中雪旺氏细胞自分泌信号的重要作用，并指出了加速髓鞘清除和改善脱髓鞘疾病的潜在机制靶标。
