Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Int J Mol Sci. 2023 Mar 30;24(7):6483. doi: 10.3390/ijms24076483.
The human nervous system exhibits limited regenerative capabilities following damage to the central nervous system (CNS), leading to a scarcity of effective treatments for nerve function recovery. In contrast, zebrafish demonstrate remarkable regenerative abilities, making them an ideal model for studying the modulation of inflammatory processes after injury. Such research holds significant translational potential to enhance our understanding of recovery from damage and disease. Macrophages play a crucial role in tissue repair and regeneration, with their subpopulations indirectly promoting axonal regeneration through developmental signals. The AP-1 signaling pathway, mediated by TNF/Tnfrsf1a, can elevate HDAC1 expression and facilitate regeneration. Furthermore, following spinal cord injury (SCI), pMN progenitors have been observed to switch between oligodendrocyte and motor neuron fates, with macrophage-secreted TNF-α potentially regulating the differentiation of ependymal-radial glia progenitors and oligodendrocytes. Radial glial cells (RGs) are also essential for CNS regeneration in zebrafish, as they perform neurogenesis and gliogenesis, with specific RG subpopulations potentially existing for the generation of neurons and oligodendrocytes. This review article underscores the critical role of macrophages and their subpopulations in tissue repair and regeneration, focusing on their secretion of TNF-α, which promotes axonal regeneration in zebrafish. We also offer insights into the molecular mechanisms underlying TNF-α's ability to facilitate axonal regeneration and explore the potential of pMN progenitor cells and RGs following SCI in zebrafish. The review concludes with a discussion of various unresolved questions in the field, and ideas are suggested for future research. Studying innate immune cell interactions with neuroglia following injury may lead to the development of novel strategies for treating the inflammatory processes associated with regenerative medicine, which are commonly observed in injury and disease.
人类神经系统在中枢神经系统 (CNS) 损伤后表现出有限的再生能力，导致神经功能恢复的有效治疗方法稀缺。相比之下，斑马鱼表现出显著的再生能力，使其成为研究损伤后炎症过程调节的理想模型。这种研究具有重要的转化潜力，可以增强我们对损伤和疾病恢复的理解。巨噬细胞在组织修复和再生中发挥着关键作用，其亚群通过发育信号间接促进轴突再生。AP-1 信号通路，由 TNF/Tnfrsf1a 介导，可以提高 HDAC1 的表达并促进再生。此外，在脊髓损伤 (SCI) 后，观察到 pMN 祖细胞在少突胶质细胞和运动神经元命运之间切换，巨噬细胞分泌的 TNF-α 可能调节室管膜-放射状胶质祖细胞和少突胶质细胞的分化。放射状胶质细胞 (RGs) 在斑马鱼的中枢神经系统再生中也很重要，因为它们进行神经发生和神经胶质发生，特定的 RG 亚群可能存在于神经元和少突胶质细胞的生成中。本文综述了巨噬细胞及其亚群在组织修复和再生中的关键作用，重点介绍了它们分泌 TNF-α，促进斑马鱼轴突再生。我们还深入探讨了 TNF-α 促进轴突再生的分子机制，并探讨了 SCI 后 pMN 祖细胞和 RGs 在斑马鱼中的潜在作用。本文总结了该领域未解决的各种问题，并提出了未来研究的思路。研究损伤后先天免疫细胞与神经胶质的相互作用可能为治疗再生医学中与炎症过程相关的策略提供新的思路，这些策略在损伤和疾病中很常见。
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