Measles virus nucleoprotein induces a regulatory immune response and reduces atherosclerosis in mice
Measles virus nucleoprotein induces a regulatory immune response and reduces atherosclerosis in mice
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DOI：
10.1161/circulationaha.107.699470
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发表时间：
2007-10-09
期刊：
影响因子：
37.8
通讯作者：
Mallat, Ziad
中科院分区：
文献类型：
--
作者：
Ait-Oufella, Hafid;Horvat, Branka;Mallat, Ziad
背景——最近的研究清楚地表明，调节性 T 细胞在控制动脉粥样硬化的免疫炎症反应中发挥着关键作用，并显着限制病变的发展。麻疹病毒感染或疫苗接种与免疫抑制有关，部分是通过麻疹病毒核蛋白诱导抗炎反应来实现的。我们假设麻疹病毒核蛋白的抗炎特性可能会限制动脉粥样硬化的发展。方法和结果 - 在此，我们首次证明，对载脂蛋白 E 缺陷小鼠重复施用麻疹病毒核蛋白可促进 1 型 T 调节细胞样抗炎反应，并抑制病变内巨噬细胞和 T 细胞的积累。麻疹病毒核蛋白治疗可显着减少新动脉粥样硬化斑块的形成，并显着抑制已形成病变的进展。核蛋白的抗动脉粥样硬化潜力保留在其短的 N 末端片段中。在淋巴细胞缺乏的小鼠中，对病变大小的保护作用消失了。 结论 - 我们的研究结果确定了麻疹病毒核蛋白通过促进调节性 T 细胞反应进行免疫调节的新机制，并表明该特性可用于治疗动脉粥样硬化，这是心脏病和中风的首要原因。
Background - Recent studies clearly suggest that regulatory T cells play a critical role in the control of the immunoinflammatory response in atherosclerosis and substantially limit lesion development. Measles virus infection or vaccination is associated with immune depression, in part through the induction of an antiinflammatory response by measles virus nucleoprotein. We hypothesized that the antiinflammatory properties of measles virus nucleoprotein may limit the development atherosclerosis.Methods and Results - Here, we show for the first time that repetitive administration of measles virus nucleoprotein to apolipoprotein E - deficient mice promotes an antiinflammatory T-regulatory- cell type 1 - like response and inhibits macrophage and T- cell accumulation within the lesions. Treatment with measles virus nucleoprotein significantly reduces the development of new atherosclerotic plaques and markedly inhibits the progression of established lesions. The antiatherosclerotic potential of nucleoprotein is retained in its short N- terminal segment. The protective effects on lesion size are lost in mice with lymphocyte deficiency.Conclusions - Our findings identify a novel mechanism of immune modulation by measles virus nucleoprotein through the promotion of a regulatory T- cell response and suggest that this property may be harnessed for treating atherosclerosis, the first cause of heart disease and stroke.