Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients
Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients
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DOI：
10.1007/s00395-014-0448-3
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发表时间：
2014-11-01
影响因子：
9.5
通讯作者：
Crea, Filippo
中科院分区：
文献类型：
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作者：
Flego, Davide;Severino, Anna;Crea, Filippo
在急性冠脉综合征(ACS)中，T细胞异常与更差的预后相关。在实验模型中，外周血白细胞表面免疫球蛋白样黏附分子CD31抑制活性的丧失被发现会加剧动脉粥样硬化。在这项研究中，我们检测了35例非ST段抬高的急性冠脉综合征患者、35例稳定型心绞痛患者和35例对照组T细胞上CD31的表达及其在TCR信号转导中的作用。此外，10名急性冠脉综合征和10名SA患者在1年的随访中进行了重新分析。流式细胞仪分析显示，在急性冠脉综合征患者中，CD31在总CD_4(+)和CD_4(+)CD28缺失(P<；0.001，急性冠脉综合征与SA)、朴素(P<；0.001，急性冠脉综合征与SA)以及中枢记忆和效应记忆CD_4(+)T细胞上的表达降低(P<；0.05，急性冠脉综合征与SA和对照组)。急性冠脉综合征患者CD31对CD4(+)和CD4(+)CD28缺失T细胞TCR信号的免疫调节作用低于SA患者(P<0.05)。随访1年时，急性冠脉综合征患者CD31的表达和功能增强，与SA相似。急性冠脉综合征患者免疫突触中CD31的募集低于对照组(P=0.012)。此外，CD31还可调节MAPK信号通路，降低Th1和Th17分化所必需的T bet和RORC-t的表达。最后，我们研究了CD31？观察到蛋白质磷酸化的不同模式的幼稚和启动的T细胞亚群。CD31介导的调节通路在SA中增强，在ACS中暂时下调。由于CD31通过提高TCR刺激阈值和T细胞分化来调节T细胞的激活，它可能是治疗急性冠脉综合征T细胞异常的一个新的分子靶点。
In acute coronary syndrome (ACS), T cell abnormalities are associated to a worse outcome. Loss of inhibitory activity of CD31, an Ig-like adhesion molecule, on peripheral leukocytes has been found to enhance atherosclerosis in experimental models. In this study, we examined the expression of CD31 on T cells, and its role on TCR signaling in 35 patients with non-ST elevation ACS, in 35 patients with stable angina (SA), and in 35 controls. Furthermore, 10 ACS and 10 SA patients were re-analyzed at 1-year follow-up. Flow-cytometry analysis showed that in ACS patients, CD31 expression was reduced on total CD4(+) and CD4(+) CD28 null (P < 0.001, ACS vs. SA), on naive (P < 0.001, ACS vs. SA) and on central-memory and effector-memory CD4(+) T cells (P < 0.05, ACS vs. SA and controls). The immunomodulatory effect of CD31 on TCR signaling of CD4(+) and CD4(+) CD28 null T cells, was lower in ACS than SA patients (P\ 0.05, for both comparisons). At 1-year follow-up, CD31 expression and function increased in ACS becoming similar to that found in SA. CD31 recruitment in the immunological synapse was lower in ACS than controls (P = 0.012). Moreover, CD31 modulated MAPK signaling and reduced the expression of T bet and Rorc-t, necessary for Th1 and Th17 differentiation. Finally, we studied TCR signaling in CD31 ? naive and primed T cell subsets observing a different pattern of protein phosphorylation. A CD31-mediated regulatory pathway is enhanced in SA and temporarily downregulated in ACS. As CD31 modulates both T cell activation, by increasing the threshold for TCR stimulation, and T cell differentiation, it might represent a novel molecular target to treat T cell abnormalities in ACS.