Increased expression of T cell immunoglobulin- and mucin domain-containing molecule-3 on natural killer cells in atherogenesis
Increased expression of T cell immunoglobulin- and mucin domain-containing molecule-3 on natural killer cells in atherogenesis
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动脉粥样硬化形成过程中自然杀伤细胞上 T 细胞免疫球蛋白和粘蛋白结构域分子 3 的表达增加
DOI：
10.1016/j.atherosclerosis.2012.02.009
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发表时间：
2012-05-01
期刊：
影响因子：
5.3
通讯作者：
Ma, Chunhong
中科院分区：
文献类型：
--
作者：
Hou, Nan;Zhao, Di;Ma, Chunhong
目的：动脉粥样硬化（AS）具有慢性炎症性疾病的许多特征，适应性免疫细胞和先天免疫细胞都在其中发挥作用。越来越多的证据表明，动脉粥样硬化中循环自然杀伤 (NK) 细胞受到损害。然而，这种损害的机制仍不清楚。我们之前报道过含有 T 细胞免疫球蛋白和粘蛋白结构域的分子 (Tim)-3 对 NK 细胞功能的抑制。在这里，我们研究了 NK 细胞上 Tim-3 的表达，并评估了其在动脉粥样硬化形成过程中 NK 损失中可能发挥的作用。方法和结果：流式细胞术分析显示 AS 患者外周 NK 细胞上的 Tim-3 表达增加。 Tim-3 表达的增加与血清脂质和炎症标志物、C 反应蛋白 (CRP) 和肿瘤坏死因子 (TNF)-α 的水平显着相关，这些都是动脉粥样硬化形成的危险因素。我们检测到 AS 患者外周 NK 细胞数量减少。 NK细胞数量与NK细胞上Tim-3表达水平和血清TNF-α水平呈显着负相关。一致的是，Tim-3 过度表达减少了 NK92 细胞数量。 Tim-3 的阻断可保护 NK92 细胞免受 TNF-α 诱导的细胞死亡。 AS 患者的外周 NK 细胞也获得了类似的结果。结论：据我们所知，我们研究的数据首次提供了证据，证明 NK 细胞上 Tim-3 表达的增强在动脉粥样硬化中 NK 细胞损失中发挥着重要作用。 NK 细胞上增强的 Tim-3 表达可用作疾病进展的指标。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Objective: Atherosclerosis (AS) has many features of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. Increasing evidence has demonstrated the impairment of circulating natural killer (NK) cells in atherosclerosis. However, the mechanisms of this impairment remain unclear. We previously reported the suppression of NK cell functions by T cell immunoglobulin- and mucin domain-containing molecule (Tim)-3. Here, we investigated the expression of Tim-3 on NK cells and assessed its possible roles in NK loss during atherogenesis.Methods and results: Flow cytometry analysis showed increased Tim-3 expression on peripheral NK cells from patients with AS. This increased expression of Tim-3 was significantly related to the levels of serum lipids and inflammation markers, C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha, which are risk factors for atherogenesis. We detected decreased peripheral NK cell number in patients with AS. The NK cell number showed significant inverse correlations with Tim-3 expression levels on NK cells and the level of serum TNF-alpha. Consistently, Tim-3 overexpression reduced NK92 cell number. Blockade of Tim-3 protected NK92 cells from TNF-alpha-induced cell death. Similar results were obtained with peripheral NK cells from patients with AS.Conclusions: To the best of our knowledge, for the first time, the data from our study provide evidence that augmented Tim-3 expression on NK cells plays an important role in NK cell loss in atherosclerosis. The augmented Tim-3 expression on NK cells might be used as an indicator for disease progression. (C) 2012 Elsevier Ireland Ltd. All rights reserved.