BACKGROUND The increase in CD4+ T cell infiltration and overproduction of CD4+ T cell-associated cytokines have been observed in the inflamed colon mucosa of patients with ulcerative colitis (UC); the underlying mechanisms are not fully understood. Survivin plays a critical role in the interference with apoptotic machinery. This study aims to elucidate the role of survivin in the interference with the apoptotic machinery in CD4+ T cells of UC patients. METHODS Peripheral blood samples were collected from UC patients (UC group) and healthy subjects (healthy group). The apoptotic status in CD4+ T cells was analyzed by flow cytometry. RESULTS We observed that the expression of survivin was significantly higher in CD4+ T cells of UC patients than in healthy subjects. UC CD4+ T cells were resistant to apoptosis induction. A complex of survivin and c-Myc, the transcription factor of FasL, was detected in CD4+ T cells in UC patients, which prevented the binding of c-Myc to the FasL promoter and interfered with the expression of FasL. Increased expression of survivin prevented the activation-induced CD4+ T cells from apoptosis. CONCLUSIONS The data indicate that UC CD4+ T cells express high levels of survivin, which impairs the apoptotic machinery in CD4+ T cells and prevents the activation-induced CD4+ T cell apoptosis. Therefore, target therapy against survivin has translational potential in the treatment of UC patients.

中文翻译：

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Survivin 损害溃疡性结肠炎患者 CD4+ T 细胞的凋亡机制。

背景 在溃疡性结肠炎 (UC) 患者发炎的结肠黏膜中观察到 CD4+ T 细胞浸润增加和 CD4+ T 细胞相关细胞因子的过度产生；潜在的机制尚未完全了解。Survivin 在干扰细胞凋亡机制中起着关键作用。本研究旨在阐明存活蛋白在干扰 UC 患者 CD4+ T 细胞凋亡机制中的作用。方法从UC患者（UC组）和健康受试者（健康组）采集外周血样本。通过流式细胞术分析 CD4+T 细胞的凋亡状态。结果我们观察到UC患者CD4+T细胞中survivin的表达明显高于健康人。UC CD4+ T 细胞对凋亡诱导具有抗性。在 UC 患者的 CD4+ T 细胞中检测到 survivin 和 FasL 的转录因子 c-Myc 的复合物，这阻止了 c-Myc 与 FasL 启动子的结合并干扰了 FasL 的表达。存活蛋白表达的增加阻止了激活诱导的 CD4+ T 细胞凋亡。结论 数据表明，UC CD4+ T 细胞表达高水平的存活蛋白，这会损害 CD4+ T 细胞的凋亡机制并阻止活化诱导的 CD4+ T 细胞凋亡。因此，针对存活蛋白的靶向治疗在 UC 患者的治疗中具有转化潜力。存活蛋白表达的增加阻止了激活诱导的 CD4+ T 细胞凋亡。结论 数据表明，UC CD4+ T 细胞表达高水平的存活蛋白，这会损害 CD4+ T 细胞的凋亡机制并阻止活化诱导的 CD4+ T 细胞凋亡。因此，针对存活蛋白的靶向治疗在 UC 患者的治疗中具有转化潜力。存活蛋白表达的增加阻止了激活诱导的 CD4+ T 细胞凋亡。结论 数据表明，UC CD4+ T 细胞表达高水平的存活蛋白，这会损害 CD4+ T 细胞的凋亡机制并阻止活化诱导的 CD4+ T 细胞凋亡。因此，针对存活蛋白的靶向治疗在 UC 患者的治疗中具有转化潜力。