Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, United States.
Elife. 2020 Dec 2;9:e60223. doi: 10.7554/eLife.60223.
Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6C monocytes infiltrate the nerve first and rapidly give way to Ly6C inflammation-resolving macrophages. In axotomized DRGs, few hematogenous leukocytes are detected and resident macrophages acquire a ramified morphology. Single-cell RNA-sequencing of injured sciatic nerve identifies five macrophage subpopulations, repair Schwann cells, and mesenchymal precursor cells. Macrophages at the nerve crush site are molecularly distinct from macrophages associated with Wallerian degeneration. In the injured nerve, macrophages 'eat' apoptotic leukocytes, a process called efferocytosis, and thereby promote an anti-inflammatory milieu. Myeloid cells in the injured nerve, but not axotomized DRGs, strongly express receptors for the cytokine GM-CSF. In GM-CSF-deficient () mice, inflammation resolution is delayed and conditioning-lesion-induced regeneration of DRG neuron central axons is abolished. Thus, carefully orchestrated inflammation resolution in the nerve is required for conditioning-lesion-induced neurorepair.
坐骨神经挤压伤会在远端神经和损伤的背根神经节 (DRG) 中引发无菌性炎症。粒细胞和促炎 Ly6C 单核细胞首先浸润神经，并迅速被 Ly6C 炎症消退的巨噬细胞取代。在损伤的 DRG 中，很少检测到血源性白细胞，而驻留巨噬细胞获得了有分支的形态。损伤的坐骨神经的单细胞 RNA 测序鉴定出五种巨噬细胞亚群、修复雪旺细胞和间充质前体细胞。神经挤压部位的巨噬细胞在分子上与与 Wallerian 变性相关的巨噬细胞不同。在损伤的神经中，巨噬细胞“吞噬”凋亡的白细胞，这一过程称为吞噬作用，从而促进抗炎环境。损伤神经中的髓样细胞，而不是损伤的 DRG，强烈表达细胞因子 GM-CSF 的受体。在 GM-CSF 缺陷 () 小鼠中，炎症消退延迟，损伤条件诱导的 DRG 神经元中枢轴突再生被消除。因此，神经中精心协调的炎症消退对于损伤条件诱导的神经修复是必需的。
