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阻塞性睡眠呼吸暂停综合征患者单核细胞亚群的再分布导致 PD-1/PD-L1 与 CD4/CD8 T 细胞的失衡对话。

Redistribution of Monocyte Subsets in Obstructive Sleep Apnea Syndrome Patients Leads to an Imbalanced PD-1/PD-L1 Cross-Talk with CD4/CD8 T Cells.

机构信息

Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, 23538 Lübeck, Germany.

Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, 23538 Lübeck, Germany

出版信息

J Immunol. 2021 Jan 1;206(1):51-58. doi: 10.4049/jimmunol.2001047. Epub 2020 Dec 2.

Abstract

Obstructive sleep apnea syndrome (OSAS) represents a substantial disease of recurrent sleep fragmentation, leading to intermittent hypoxia and subsequent diseases such as cardiovascular, metabolic, or cognitive dysfunctions. In addition, OSAS is considered as low-grade systemic inflammation, which is associated with a higher incidence of cancer, severity of infections, and an overall immune dysregulation. This research project aims to comprehensively investigate the interplay of wholesome sleep and the immune functions of circulating monocytes and T cells in OSAS patients, which are known to be affected by oxidative stress. We studied the distribution of the CD14/CD16 characterized monocyte subsets in peripheral blood as well as their PD-L1 expression and complex formation with T cells. Furthermore, a detailed analysis of T cell subsets with regard to their PD-1 and PD-L1 expression was performed. Data revealed a decrease of classical monocytes accompanied by an increase of both CD16 monocyte subsets in OSAS patients that was positively correlated with the body mass index. OSAS patients revealed an increased PD-1 and PD-L1 expression in T cells and monocytes, respectively, which was linked to the severity of monocyte subset alterations. The complex formation of monocytes and T cells was also elevated in OSAS patients, which indicates a deregulated PD-1/PD-L1 cross-talk between these cells. Our data show for the first time, to our knowledge, massive alterations of peripheral monocyte subsets in response to OSAS and its accompanying phenomena.

摘要

阻塞性睡眠呼吸暂停综合征(OSAS)是一种严重的睡眠碎片化疾病,导致间歇性缺氧,并随后引发心血管、代谢或认知功能障碍等疾病。此外,OSAS 被认为是低度全身炎症,与癌症发病率升高、感染严重程度以及整体免疫失调有关。本研究项目旨在全面研究健康睡眠与 OSAS 患者循环单核细胞和 T 细胞免疫功能的相互作用,已知氧化应激会影响这些细胞。我们研究了外周血中 CD14/CD16 特征性单核细胞亚群的分布及其 PD-L1 表达和与 T 细胞的复合物形成。此外,还对 T 细胞亚群进行了详细的 PD-1 和 PD-L1 表达分析。研究结果显示,OSAS 患者的经典单核细胞数量减少,同时两种 CD16 单核细胞亚群数量增加,这与体重指数呈正相关。OSAS 患者的 T 细胞和单核细胞中 PD-1 和 PD-L1 的表达均增加,这与单核细胞亚群改变的严重程度有关。OSAS 患者单核细胞和 T 细胞之间的复合物形成也增加,表明这些细胞之间的 PD-1/PD-L1 相互作用失调。我们的数据首次表明,OSAS 及其伴随现象会引起外周单核细胞亚群的大量改变。

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