Respirology:阻塞性睡眠呼吸暂停患者的PD-L1水平的分析

2019-07-23 不详 MedSci原创

在阻塞性睡眠呼吸暂停(OSA)患者中,间歇性缺氧(IH)会导致程序性上调细胞死亡-1(PD-1)受体及其配体(PD-L1)而损害免疫监视。由于OSA相关癌症的风险取决于年龄,我们评估了中年和老年OSA患者以及小鼠模型中PD-L1 / PD-1的表达水平的差异。

背景和目标
在阻塞性睡眠呼吸暂停(OSA)患者中,间歇性缺氧(IH)会导致程序性上调细胞死亡-1(PD-1)受体及其配体(PD-L1)而损害免疫监视。由于OSA相关癌症的风险取决于年龄,我们评估了中年和老年OSA患者以及小鼠模型中PD-L1 / PD-1的表达水平的差异。

方法
研究人员将41名患有严重OSA和40名健康志愿者(HV)的患者根据年龄(≤55岁和> 55岁)分为两组,进行PD-L1表达研究,主要采用的方法是流式细胞术,定量PCR(qPCR)和ELISA以确定单核细胞上的PD-L1表达和血浆PD-L1蛋白水平。此外,我们用老鼠和年轻小鼠分析了体内IH模型中的PD-L1表达。

结果
在大于55岁的受试者中,与HV相比,严重OSA会增加单核细胞上的PD-L1表面蛋白和mRNA水平表达以及血浆中可溶性PD-L1蛋白浓度。PD-L1和缺氧诱导因子(HIF)-1α表达与HV的年龄相关。在暴露于IH的小鼠中,F4 / 80 +脾细胞上的PD-L1表达也仅在幼小动物中增加。在55岁以下的受试者中,OSA患者的HIF-1α表达显着高于HV患者,而单核细胞中的PD-L1表达与年轻OSA患者的HIF-1α表达有关。

结论
由于HIF-1α激活,OSA患者的PD-L1上调主要发生在年轻患者中。在患有OSA的老年患者中,未检测到上调,可能是由于氧敏感性受损导致的。

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    2020-04-18 tomyang96
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    2019-07-25 smartjoy
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