Antigen-Presenting Cell-Like Neutrophils Foster T Cell Response in Hyperlipidemic Patients and Atherosclerotic Mice.
Antigen-Presenting Cell-Like Neutrophils Foster T Cell Response in Hyperlipidemic Patients and Atherosclerotic Mice.
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抗原呈递细胞样中性粒细胞促进高脂血症患者和动脉粥样硬化小鼠的 T 细胞反应
DOI：
10.3389/fimmu.2022.851713
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Zhao T;Jiang Q;Li W;Wang Y;Zou Y;Chai X;Yuan Z;Ma L;Yu R;Deng T;Yu C;Wang T
中性粒细胞构成动脉粥样硬化斑块中丰富的细胞成分。目前的研究大多集中在中性粒细胞释放的颗粒蛋白在动脉粥样硬化中的作用。在这里，我们揭示了一个独特的中性粒细胞亚群，它在动脉粥样硬化中表现出抗原提呈细胞(APC)(后来被称为APC样中性粒细胞)的特征。研究APC样中性粒细胞在高脂血症患者和动脉粥样硬化小鼠中的作用及相关机制。高脂血症患者外周血中中性粒细胞和APC样中性粒细胞的百分率高于健康对照组。同时，我们还发现在动脉粥样硬化的小鼠中性粒细胞和APC样中性粒细胞有较高的渗透。氧化低密度脂蛋白诱导佛波醇-12-肉豆蔻酸酯-13-醋酸酯(PMA)激活的中性粒细胞获得APC样表型。重要的是，中性粒细胞通过高表达APC样标志物，获得APC功能，通过HLADR/CD80CD86促进CD3+T细胞的增殖和干扰素γ的产生。与体外研究结果一致，高脂血症患者中性粒细胞与CD3+T细胞呈正相关。总之，我们的工作在高脂血症患者和动脉粥样硬化小鼠中都发现了促炎性中性粒细胞亚群。这种独特的中性粒细胞表型可以激活适应性免疫反应，促进动脉粥样硬化的进展。因此，这个中性粒细胞亚群可能成为动脉粥样硬化免疫治疗的新靶点。
Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis. The roles of APC-like neutrophils and relevant mechanisms were investigated in hyperlipidemic patients and atherosclerotic mice. Higher percentages of neutrophils and APC-like neutrophils were found in peripheral blood of hyperlipidemic patients than that of healthy donors. Meanwhile, we also identified higher infiltration of neutrophils and APC-like neutrophils in atherosclerotic mice. Ox-LDL induced Phorbol-12-myristate-13-acetate (PMA)-activated neutrophils to acquire the APC-like phenotype. Importantly, upon over-expression of APC-like markers, neutrophils acquired APC functions to promote the proliferation and interferon-γ production of CD3+ T cells via HLA-DR/CD80/CD86. In accordance with what found in vitro, positive correlation between neutrophils and CD3+ T cells was observed in hyperlipidemic patients. In conclusion, our work identifies a proinflammatory neutrophil subset in both hyperlipidemic patients and atherosclerotic mice. This unique phenotype of neutrophils could activate the adaptive immune response to promote atherosclerosis progression. Thus, this neutrophil subset may be a new target for immunotherapy of atherosclerosis.
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影响因子：
20.1
作者：
Kobiyama K;Ley K
通讯作者：
Ley K
影响因子：
16.6
作者：
Alabi A;Xia XD;Gu HM;Wang F;Deng SJ;Yang N;Adijiang A;Douglas DN;Kneteman NM;Xue Y;Chen L;Qin S;Wang G;Zhang DW
通讯作者：
Zhang DW
影响因子：
81.5
作者：
Libby, Peter;Buring, Julie E.;Lewis, Eldrin F.
通讯作者：
Lewis, Eldrin F.
影响因子：
15.9
作者：
Koltsova, Ekaterina K.;Garcia, Zacarias;Ley, Klaus
通讯作者：
Ley, Klaus
影响因子：
3.7
作者：
Hufford MM;Richardson G;Zhou H;Manicassamy B;García-Sastre A;Enelow RI;Braciale TJ
通讯作者：
Braciale TJ