Träger Ulrike, Magnusson Anna, Lahiri Swales Nayana, Wild Edward, North Janet, Lowdell Mark, Björkqvist Maria
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK.
Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
PLoS Curr. 2013 Dec 13;5:ecurrents.hd.5791c897b5c3bebeed93b1d1da0c0648. doi: 10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648.
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral innate immune activation have been described as features of the disease. Isolated human HD monocytes have been shown to produce more cytokines upon LPS stimulation compared to control monocytes. Understanding alterations in the signalling cascades responsible and activated by this increase in pro-inflammatory cytokine production is crucial in understanding the molecular basis of this phenomenon. Here we investigated the signalling cascade most commonly activated by pro-inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow cytometry, we show that one out of three key transcription factors activated by JAK/STAT signalling is altered in primary human HD innate immune cells, suggesting that this pathway may only play a minor, additive role in the immune cell dysfunction in HD.
亨廷顿舞蹈症（HD）是一种由亨廷顿（HTT）基因中CAG重复序列扩增引起的遗传性神经退行性疾病。中枢和外周先天性免疫激活均被描述为该疾病的特征。与对照单核细胞相比，分离出的人类HD单核细胞在脂多糖（LPS）刺激下可产生更多细胞因子。了解负责并由促炎细胞因子产生增加所激活的信号级联变化，对于理解这一现象的分子基础至关重要。在此，我们研究了最常由促炎细胞因子（如IL-6）激活的信号级联——JAK/STAT信号级联。使用流式细胞术，我们发现JAK/STAT信号激活的三个关键转录因子中有一个在原代人类HD先天性免疫细胞中发生了改变，这表明该途径在HD免疫细胞功能障碍中可能仅起次要的、附加的作用。
