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In vivo neutralization of the protagonist role of macrophages during the chronic inflammatory stage of Huntington’s disease

机译:在亨廷顿疾病慢性炎症期间巨噬细胞的主角中和在体内中和的主体作用

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Neurodegenerative diseases, characterised by the progressive and selective neuronal death in the central nervous system, are frequently accompanied by an activated immune system. In Huntington’s disease (HD), clinical and animal studies show evidence of immune activity, along with hyper-reactive monocyte/macrophage responses, while application of immunosuppressive regimens have imparted beneficial effects to HD mice. These findings suggest a contributory role of the immune system in HD pathology, with immune-based interventions offering a potential therapeutic strategy. Herein, we show that peripheral and CNS immune system activity increased with disease progression in HD mouse models and defined the phenotype of the immune response. Additionally, the depletion of monocytes and macrophages in vivo, via clodronate liposome treatment, revealed a major contributory role of these innate immune cells to the chronic inflammatory milieu observed during the course of the disease. This suggests that peripheral immunomodulatory strategies targeting monocytes and macrophages could be relevant for HD.
机译:神经退行性疾病,其特征在于中枢神经系统中的渐进性和选择性神经元死亡,经常伴有活化的免疫系统。在亨廷顿的疾病(HD)中,临床和动物研究表明免疫活性的证据,以及超反应性单核细胞/巨噬细胞反应,而免疫抑制方案的施用赋予高清小鼠的有益作用。这些研究结果表明免疫系统在高清病理学中的作用,具有潜在的治疗策略的免疫介入。在此,我们表明外周和CNS免疫系统活性随着HD小鼠模型中的疾病进展而增加,并定义了免疫应答的表型。此外,通过克莱膦酸盐脂质体处理耗尽了体内单核细胞和巨噬细胞,揭示了这些先天免疫细胞对疾病过程中观察到的慢性炎症内部的主要作用作用。这表明靶向单核细胞和巨噬细胞的外周免疫调节策略可能与HD相关。

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