State Key Laboratory of Animal Biotech Breeding, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
National Institute of Biological Sciences, Beijing, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.
Cell Rep. 2024 Feb 27;43(2):113753. doi: 10.1016/j.celrep.2024.113753. Epub 2024 Feb 10.
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.
巨噬细胞向受损神经的募集引发了一系列事件，包括髓鞘碎片清除和神经营养因子的分泌，这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。在这里，我们通过比较野生型与 Mlkl 和 Sarm1 两种在外周神经损伤后髓鞘碎片清除受损的小鼠品系，鉴定出白细胞介素 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 以自分泌的方式起作用，并与白细胞介素 17 受体 B 结合，促进巨噬细胞的募集，而全身或雪旺细胞特异性的 IL-17B 缺失会减少巨噬细胞浸润、髓鞘清除和轴突再生。我们还表明，IL-17B 信号通路在损伤的中枢神经中存在缺陷。这些结果揭示了施万细胞自分泌信号在 Wallerian 变性过程中的重要作用，并指出了加速髓鞘清除和改善脱髓鞘疾病的潜在机制靶点。
