Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston, TX 77030, USA.
Exp Neurol. 2020 Jun;328:113259. doi: 10.1016/j.expneurol.2020.113259. Epub 2020 Feb 24.
Neuroinflammation is increasingly recognized as an important mediator of disease progression in patients with amyotrophic lateral sclerosis (ALS). Recent research suggests that pro-inflammatory microglia in ALS mice promote motoneuron cytotoxicity by secreting reactive oxygen species and pro-inflammatory cytokines. Gene expression analyses indicate that peripheral circulating monocytes from ALS patients are skewed towards a pro-inflammatory state that contributes to ALS disease progression. Better understanding of macrophage phenotypes of ALS patients is therefore warranted. In this study, we demonstrate that M1 macrophages differentiated from ALS circulating monocytes produced more pro-inflammatory cytokines, including IL-6 and TNFα, than M1 macrophages derived from healthy control monocytes. More importantly, IL-6 protein levels of ALS M1 macrophages positively correlated with disease burden, and TNFα protein levels of ALS M1 macrophages positively correlate with disease progression rates. Collectively, these data suggest that monocytes from ALS patients are more readily activated and differentiated to a pro-inflammatory M1 phenotype, and represent a potential target for immunomodulatory therapy.
神经炎症越来越被认为是肌萎缩侧索硬化症（ALS）患者疾病进展的重要介质。最近的研究表明，ALS 小鼠中的促炎小胶质细胞通过分泌活性氧和促炎细胞因子来促进运动神经元的细胞毒性。基因表达分析表明，来自 ALS 患者的外周循环单核细胞偏向于促炎状态，这有助于 ALS 疾病的进展。因此，更深入地了解 ALS 患者的巨噬细胞表型是有必要的。在这项研究中，我们证明了从 ALS 循环单核细胞分化而来的 M1 巨噬细胞产生了更多的促炎细胞因子，包括 IL-6 和 TNFα，而从健康对照组单核细胞分化而来的 M1 巨噬细胞则产生了较少的促炎细胞因子。更重要的是，ALS M1 巨噬细胞的 IL-6 蛋白水平与疾病负担呈正相关，而 ALS M1 巨噬细胞的 TNFα 蛋白水平与疾病进展速度呈正相关。总的来说，这些数据表明，来自 ALS 患者的单核细胞更容易被激活并分化为促炎的 M1 表型，这代表了免疫调节治疗的一个潜在靶点。
