Abstract:
Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, following rapid recruitment to the injured spinal cord, neutrophils mostly reverse migrate throughout the zebrafish body. In addition, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-α expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.
摘要:
脊髓损伤会在非再生哺乳动物和再生斑马鱼中引发强烈的先天炎症反应。中性粒细胞是第一个被招募到损伤部位的免疫群体。然而,它们在修复过程中的作用,特别是在再生环境中,仍然很大程度上未知。这里,我们证明,在快速招募受伤的脊髓后,中性粒细胞大部分反向迁移到斑马鱼体内。此外,通过抑制Cxcr4促进中性粒细胞炎症消退促进细胞和功能再生。中性粒细胞特异性RNA-seq分析揭示了与巨噬细胞/小胶质细胞群体中tnf-α表达的瞬时增加相关的增强的活化状态。相反,通过Cxcr1/2抑制阻断中性粒细胞募集可减少损伤部位巨噬细胞/小胶质细胞的存在,并损害脊髓再生.总之,这些发现为中性粒细胞在脊髓再生中的作用提供了新的见解,强调其免疫谱对修复过程结果的显著影响。