Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function
Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function
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DOI：
10.1038/ni1373
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发表时间：
2006-09-01
影响因子：
30.5
通讯作者：
Hirano, Toshio
中科院分区：
文献类型：
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作者：
Kitamura, Hidemitsu;Morikawa, Hideyuki;Hirano, Toshio
锌是一种微量元素，对许多酶和转录因子的功能至关重要。锌缺乏导致先天和获得性免疫反应缺陷。然而，人们对锌影响免疫细胞功能的机制知之甚少。本研究表明，toll样受体4激动剂脂多糖（LPS）刺激改变了树突状细胞中锌转运蛋白的表达，从而减少了细胞内游离锌。锌螯合剂可以模拟LPS的作用，而锌补充剂或锌转运蛋白Zip6基因的过度表达可以抑制LPS诱导的主要组织相容性复合物II类和共刺激分子的上调。Zip6是一种锌转运蛋白，其表达被LPS降低。这些结果建立了toll样受体信号和锌稳态之间的联系。
Zinc is a trace element that is essential for the function of many enzymes and transcription factors. Zinc deficiency results in defects in innate and acquired immune responses. However, little is known about the mechanism(s) by which zinc affects immune cell function. Here we show that stimulation with the Toll-like receptor 4 agonist lipopolysaccharide (LPS) altered the expression of zinc transporters in dendritic cells and thereby decreased intracellular free zinc. A zinc chelator mimicked the effects of LPS, whereas zinc supplementation or overexpression of the gene encoding Zip6, a zinc transporter whose expression was reduced by LPS, inhibited LPS-induced upregulation of major histocompatibility complex class II and costimulatory molecules. These results establish a link between Toll-like receptor signaling and zinc homeostasis.