Volchenkov Roman, Nygaard Vegard, Sener Zeynep, Skålhegg Bjørn Steen
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital HF - Radiumhospitalet, Montebello, Oslo, Norway.
Front Immunol. 2017 Jun 19;8:698. doi: 10.3389/fimmu.2017.00698. eCollection 2017.
The IL-17-producing CD4 T helper cell (Th17) differentiation is affected by stimulation of the aryl hydrocarbon receptor (AhR) pathway and by hypoxia-inducible factor 1 alpha (HIF-1α). In some cases, Th17 become non-pathogenic and produce IL-10. However, the initiating events triggering this phenotype are yet to be fully understood. Here, we show that such cells may be differentiated at low oxygen and regardless of AhR ligand treatment such as cigarette smoke extract. Hypoxia led to marked alterations of the transcriptome of IL-10-producing Th17 cells affecting genes involved in metabolic, anti-apoptotic, cell cycle, and T cell functional pathways. Moreover, we show that oxygen regulates the expression of CD52, which is a cell surface protein that has been shown to suppress the activation of other T cells upon release. Taken together, these findings suggest a novel ability for Th17 cells to regulate immune responses in an oxygen-dependent fashion.
产生白细胞介素-17的CD4辅助性T细胞（Th17）的分化受芳烃受体（AhR）途径的刺激以及缺氧诱导因子1α（HIF-1α）的影响。在某些情况下，Th17会变成非致病性的并产生白细胞介素-10。然而，引发这种表型的起始事件尚未完全明确。在此，我们表明这类细胞可能在低氧条件下分化，且与AhR配体处理（如香烟烟雾提取物）无关。缺氧导致产生白细胞介素-10的Th17细胞的转录组发生显著改变，影响参与代谢、抗凋亡、细胞周期和T细胞功能途径的基因。此外，我们表明氧气调节CD52的表达，CD52是一种细胞表面蛋白，已被证明在释放后可抑制其他T细胞的激活。综上所述，这些发现提示Th17细胞具有以氧依赖方式调节免疫反应的新能力。
