Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses Cimi-Paris, Paris, France.
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY.
J Exp Med. 2020 Nov 2;217(11). doi: 10.1084/jem.20200471.
Wallerian degeneration (WD) is a process of autonomous distal degeneration of axons upon injury. Macrophages (MPs) of the peripheral nervous system (PNS) are the main cellular agent controlling this process. Some evidence suggests that resident PNS-MPs along with MPs of hematogenous origin may be involved, but whether these two subsets exert distinct functions is unknown. Combining MP-designed fluorescent reporter mice and coherent anti-Stokes Raman scattering (CARS) imaging of the sciatic nerve, we deciphered the spatiotemporal choreography of resident and recently recruited MPs after injury and unveiled distinct functions of these subsets, with recruited MPs being responsible for efficient myelin stripping and clearance and resident MPs being involved in axonal regrowth. This work provides clues to tackle selectively cellular processes involved in neurodegenerative diseases.
Wallerian 变性（WD）是一种损伤后轴突自主远端变性的过程。周围神经系统（PNS）中的巨噬细胞（MPs）是控制这一过程的主要细胞因子。有证据表明，固有 PNS-MPs 与血液来源的 MPs 可能都参与其中，但这两个亚群是否发挥不同的功能尚不清楚。我们结合设计了荧光报告基因的 MPs 小鼠和坐骨神经的相干反斯托克斯拉曼散射（CARS）成像，解析了损伤后固有和新募集的 MPs 的时空编排，并揭示了这两个亚群的不同功能，募集的 MPs 负责有效的髓鞘剥落和清除，而固有 MPs 则参与轴突再生。这项工作为有针对性地研究参与神经退行性疾病的细胞过程提供了线索。
