Circulating CD4+ CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease
Circulating CD4+ CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease
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DOI：
10.1016/j.intimp.2017.09.028
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发表时间：
2017-11-01
影响因子：
5.6
通讯作者：
Liang, Chun
中科院分区：
文献类型：
--
作者：
Ding, Ru;Gao, Wenwu;Liang, Chun
冠状动脉疾病（coronary artery disease，CAD）是心血管疾病的一种常见亚型。主要的促成事件是动脉粥样硬化，这是一种进行性炎症状态，导致动脉壁增厚和动脉粥样硬化斑块的形成。最近的证据表明，循环中的CD 4（+）CXCR 5（+）T细胞可以促进炎症反应。在这项研究中，检查了CAD患者循环CD 4 + CXCR 5 + T细胞的频率、表型和功能。数据显示，CAD患者的循环CD 4（+）CXCR 5（+）T细胞富含PD-1（+）CCR 7（-）亚群，该亚群先前被确定为B细胞帮助中最有效的亚群。CAD患者的CD 4（+）CXCR 5（+）T细胞分泌的IFN-γ、IL-17 A和IL-21水平也显著高于健康对照组。消耗PD-1（+）群体显著降低了细胞因子分泌。有趣的是，CD 4（+）CXCR 5（+）PD-1（-）T细胞在抗CD 3/CD 28或SEB刺激后显著上调PD-1。来自CAD患者的CD 4（+）CXCR 5（+）T细胞也表现出比来自健康个体的那些更强的刺激B细胞炎症的能力。与CAD来源的CD 4（+）CXCR 5（+）T细胞共同孵育的B细胞中STAT 1和STAT 3的磷酸化水平显著高于对照组。在与来自CAD的CD 4（+）CXCR 5（+）T细胞孵育的B细胞中，IL-6和IFN-γ表达也显著更高。总之，这项研究表明，CAD患者呈现出高度活化的CD 4（+）CXCR 5（+）T细胞亚群，可能以多种方式促进促炎反应。因此，应在CAD患者中检查使用CD 4（+）CXCR 5（+）T细胞作为治疗靶点的可能性。
Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4(+) CXCR5(+) T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4+ CXCR5+ T cells in CAD patients were examined. Data showed that circulating CD4(+) CXCR5(+) T cells in CAD patients were enriched with a PD-1(+) CCR7(-) subset, which was previously identified as the most potent in B cell help. The CD4(+) CXCR5(+) T cells in CAD patients also secreted significantly higher levels of IFN-gamma, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1(+) population significantly reduced the cytokine secretion. Interestingly, the CD4(+) CXCR5(+) PD-1(-) T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4(+) CXCR5(+) T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4(+) CXCR5(+) T cells from CAD than controls. The IL-6 and IFN-gamma expression were also significantly higher in B cells incubated with CD4(+) CXCR5(+) T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4(+) CXCR5(+) T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4(+) CXCR5(+) T cells as a therapeutic target should therefore be examined in CAD patients.