Wild-type huntingtin regulates human macrophage function.
Wild-type huntingtin regulates human macrophage function.
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野生型亨廷顿蛋白调节人巨噬细胞功能。
DOI：
10.1038/s41598-020-74042-8
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发表时间：
2020-10-14
影响因子：
4.6
通讯作者：
Andre R
中科院分区：
文献类型：
--
作者：
O'Regan GC;Farag SH;Ostroff GR;Tabrizi SJ;Andre R
亨廷顿蛋白(HTT)的突变形式是遗传性神经退行性疾病亨廷顿病的原因。除了对中枢神经系统的影响外，疾病相关突变HTT还会导致髓系固有免疫系统细胞，即单核细胞和巨噬细胞的异常表型。然而，该蛋白的野生型是否在正常的人类巨噬细胞功能中起作用还没有确定。在这里，研究了降低野生型(Wt)HTT的表达对来自健康、非疾病受试者的原代单核细胞来源的巨噬细胞功能的影响。这证明了wtHTT在维持正常巨噬细胞健康和功能方面的先前未被描述的作用。例如，wtHTT表达的降低与诱导的细胞因子的释放减少、吞噬功能增强以及对细胞应激的易感性增加有关。考虑到亨廷顿病中主要与巨噬细胞功能障碍有关的细胞内信号通路没有任何影响，这些变化很可能通过不同于与蛋白质突变形式相关的机制发生。
The huntingtin (HTT) protein in its mutant form is the cause of the inherited neurodegenerative disorder, Huntington’s disease. Beyond its effects in the central nervous system, disease-associated mutant HTT causes aberrant phenotypes in myeloid-lineage innate immune system cells, namely monocytes and macrophages. Whether the wild-type form of the protein, however, has a role in normal human macrophage function has not been determined. Here, the effects of lowering the expression of wild-type (wt)HTT on the function of primary monocyte-derived macrophages from healthy, non-disease human subjects were examined. This demonstrated a previously undescribed role for wtHTT in maintaining normal macrophage health and function. Lowered wtHTT expression was associated, for instance, with a diminished release of induced cytokines, elevated phagocytosis and increased vulnerability to cellular stress. These may well occur by mechanisms different to that associated with the mutant form of the protein, given an absence of any effect on the intracellular signalling pathway predominantly associated with macrophage dysfunction in Huntington’s disease.
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影响因子：
25
作者：
Lo Sardo, Valentina;Zuccato, Chiara;Cattaneo, Elena
通讯作者：
Cattaneo, Elena
影响因子：
4.7
作者：
Dobson L;Träger U;Farmer R;Hayardeny L;Loupe P;Hayden MR;Tabrizi SJ
通讯作者：
Tabrizi SJ
DOI：
10.1073/pnas.0800137105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Lieu, Zi Zhao;Lock, John G.;Gleeson, Paul A.
通讯作者：
Gleeson, Paul A.
影响因子：
4.3
作者：
Brandstaetter H;Kruppa AJ;Buss F
通讯作者：
Buss F
影响因子：
4.7
作者：
Leavitt, BR;van Raamsdonk, JM;Hayden, MR
通讯作者：
Hayden, MR