美国俄亥俄州立大学韦克斯纳医学中心Benjamin M. Segal团队近期取得重要工作进展。他们研究提出，细胞因子极化、选择性激活的骨髓中性粒细胞驱动轴突再生。相关研究成果2024年5月29日在线发表于《自然—免疫学》杂志上。

据介绍，成人中枢神经系统（CNS）具有有限的自我修复能力。切断的中枢神经系统轴突通常不能再生。对旨在增强神经元活力、促进轴突再生并最终恢复受创伤中枢神经系统损伤、多发性硬化症、中风和其他神经疾病影响的个体失去的神经功能的治疗需求尚未得到满足。

研究人员证明，当用重组白细胞介素-4（IL-4）和粒细胞集落刺激因子（G-CSF）的组合极化时，小鼠和人骨髓中性粒细胞都上调了替代的激活标记物，并产生了一系列生长因子，从而获得了促进轴突生长的能力。

此外，将IL-4/G-CSF极化的骨髓中性粒细胞过继转移到中枢神经系统损伤的实验模型中，触发了视神经和脊髓内的大量轴突再生。这些发现对基于自体骨髓细胞的疗法的未来发展具有深远的意义，这可能使研究者们更接近于逆转中枢神经系统损伤的有效解决方案

附：英文原文

Title: Cytokine polarized, alternatively activated bone marrow neutrophils drive axon regeneration

Author: Jerome, Andrew D., Sas, Andrew R., Wang, Yan, Hammond, Luke A., Wen, Jing, Atkinson, Jeffrey R., Webb, Amy, Liu, Tom, Segal, Benjamin M.

Issue&Volume: 2024-05-29

Abstract: The adult central nervous system (CNS) possesses a limited capacity for self-repair. Severed CNS axons typically fail to regrow. There is an unmet need for treatments designed to enhance neuronal viability, facilitate axon regeneration and ultimately restore lost neurological functions to individuals affected by traumatic CNS injury, multiple sclerosis, stroke and other neurological disorders. Here we demonstrate that both mouse and human bone marrow neutrophils, when polarized with a combination of recombinant interleukin-4 (IL-4) and granulocyte colony-stimulating factor (G-CSF), upregulate alternative activation markers and produce an array of growth factors, thereby gaining the capacity to promote neurite outgrowth. Moreover, adoptive transfer of IL-4/G-CSF-polarized bone marrow neutrophils into experimental models of CNS injury triggered substantial axon regeneration within the optic nerve and spinal cord. These findings have far-reaching implications for the future development of autologous myeloid cell-based therapies that may bring us closer to effective solutions for reversing CNS damage.

DOI: 10.1038/s41590-024-01836-7

Source: https://www.nature.com/articles/s41590-024-01836-7