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单核细胞抑制 NK 活性 TGF-β 在阻塞性睡眠呼吸暂停患者中。

Monocytes inhibit NK activity TGF-β in patients with obstructive sleep apnoea.

机构信息

The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.

CIBER of Respiratory Diseases (CIBERES), Madrid, Spain.

出版信息

Eur Respir J. 2017 Jun 15;49(6). doi: 10.1183/13993003.02456-2016. Print 2017 Jun.

Abstract

Obstructive sleep apnoea (OSA) is associated with cancer incidence and mortality. The contribution of the immune system appears to be crucial; however, the potential role of monocytes and natural killer (NK) cells remains unclear.Quantitative reverse transcriptase PCR, flow cytometry and assays were used to analyse the phenotype and immune response activity in 92 patients with OSA (60 recently diagnosed untreated patients and 32 patients after 6 months of treatment with continuous positive airway pressure (CPAP)) and 29 healthy volunteers (HV).We determined that monocytes in patients with OSA exhibit an immunosuppressive phenotype, including surface expression of glycoprotein-A repetitions predominant protein (GARP) and transforming growth factor-β (TGF-β), in contrast to those from the HV and CPAP groups. High levels of TGF-β were detected in OSA sera. TGF-β release by GARP monocytes impaired NK cytotoxicity and maturation. This altered phenotype correlated with the hypoxic severity clinical score (CT90). Reoxygenation eventually restored the altered phenotypes and cytotoxicity.This study demonstrates that GARP monocytes from untreated patients with OSA have an NK-suppressing role through their release of TGF-β. Our findings show that monocyte plasticity immunomodulates NK activity in this pathology, suggesting a potential role in cancer incidence.

摘要

阻塞性睡眠呼吸暂停(OSA)与癌症发病率和死亡率有关。免疫系统的贡献似乎至关重要;然而,单核细胞和自然杀伤(NK)细胞的潜在作用仍不清楚。使用定量逆转录聚合酶链反应、流式细胞术和测定法分析了 92 例 OSA 患者(60 例最近诊断未经治疗的患者和 32 例接受持续气道正压通气(CPAP)治疗 6 个月的患者)和 29 名健康志愿者(HV)的表型和免疫反应活性。我们确定 OSA 患者的单核细胞表现出免疫抑制表型,包括糖蛋白-A 重复主要蛋白(GARP)和转化生长因子-β(TGF-β)的表面表达,与 HV 和 CPAP 组相比。OSA 血清中检测到高水平的 TGF-β。GARP 单核细胞释放的 TGF-β损害 NK 细胞毒性和成熟。这种改变的表型与缺氧严重程度临床评分(CT90)相关。再氧化最终恢复了改变的表型和细胞毒性。这项研究表明,未经治疗的 OSA 患者的 GARP 单核细胞通过释放 TGF-β发挥抑制 NK 的作用。我们的研究结果表明,单核细胞可塑性在这种病理中调节 NK 活性,提示其在癌症发病率中可能具有作用。

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