法国脑研究所-巴黎脑研究所-ICM Séverine Boillée 研究组取得最新进展。他们的研究发现修饰外周巨噬细胞具有改变小胶质细胞反应性和延长肌萎缩性侧索硬化症（ALS）存活的能力。2020年10月19日，《自然-神经科学》杂志发表了这一成果。

他们显示，在小鼠模型和ALS患者中，沿周围运动神经元轴突的巨噬细胞能对神经退行作出反应。在ALS小鼠中，外周髓样细胞浸润进入脊髓受到限制，并取决于疾病持续时间。使用细胞替换，ALS小鼠外周血髓细胞中活性氧途径的靶向基因调节，减少了外周巨噬细胞和小胶质细胞的活化，延迟了症状并提高了存活率。

转录组学研究表明，坐骨神经巨噬细胞和小胶质细胞对神经变性的反应不同，巨噬细胞的瞬时时间变化与进程以及小胶质细胞的单向激活。修饰外周巨噬细胞抑制了促炎性小胶质细胞反应，并转向神经元支持。因此，在外周修饰巨噬细胞具有影响疾病进展的能力，并且可能对ALS具有治疗价值。

研究人员表示，小胶质细胞和外周巨噬细胞均与ALS有关，尽管它们各自的作用尚未确定。

附：英文原文

Title: Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival

Author: Aude Chiot, Sakina Zadi, Charlne Iltis, Matthieu Ribon, Flix Berriat, Lorenzo Schiaffino, Ariane Jolly, Pierre de la Grange, Michel Mallat, Delphine Bohl, Stphanie Millecamps, Danielle Seilhean, Christian S. Lobsiger, Sverine Boille

Issue&Volume: 2020-10-19

Abstract: Microglia and peripheral macrophages have both been implicated in amyotrophic lateral sclerosis (ALS), although their respective roles have yet to be determined. We now show that macrophages along peripheral motor neuron axons in mouse models and patients with ALS react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and depended on disease duration. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted differently to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a shift toward neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and may be of therapeutic value for ALS. Peripheral macrophages located along motor axons react differently to neurodegeneration compared to CNS microglia in ALS mice. Modifying peripheral macrophages suppresses proinflammatory microglial responses, shifting them toward neuronal support.

DOI: 10.1038/s41593-020-00718-z

Source: https://www.nature.com/articles/s41593-020-00718-z