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首页> 外文期刊>Biological chemistry >Role of hypoxia inducible factor-la for interferon synthesis in mouse dendritic cells
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Role of hypoxia inducible factor-la for interferon synthesis in mouse dendritic cells

机译:低氧诱导因子-Ia在小鼠树突状细胞中干扰素合成中的作用

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摘要

Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1alpha in bone marrow-derived DCs from wild type and mye-loid-specific HIF-1alpha knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cyto-sine-phosphatidyl-guanines significantly induce HIF-la mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1alpha protein is needed for adequate production of interferon-a and -beta. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-la protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-la plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.
机译:树突状细胞(DC)是先天免疫与适应性免疫之间的重要纽带。 DC在氧气张力通常较低的发炎组织中被激活,这需要转录因子低氧诱导因子(HIF)-1才能实现细胞适应。为了研究HIF-1转录复合物是否在DC的功能中起关键作用,我们比较了外源性炎症刺激和低氧对来自野生型和髓样特异性HIF-的骨髓DC的HIF-1alpha的影响。 1alpha敲除小鼠。我们显示,Toll样受体配体脂多糖和细胞正弦磷脂酰鸟嘌呤能显着诱导HIF-1αmRNA和蛋白质,从而导致血管内皮生长因子的HIF-1靶基因表达升高。相反,聚肌苷酸:聚胞苷酸没有显示出可比的效果。此外,上调炎症细胞因子的潜力严重影响DC功能。我们的数据表明,HIF-1alpha蛋白是产生干扰素-a和-beta所需的。在DC和细胞毒性T细胞的共培养物中,我们观察到缺乏活性HIF-1α蛋白的DC在T细胞中诱导的CD278和颗粒酶B mRNA明显更少。我们得出的结论是,HIF-1α在直流干扰素产生和T细胞活化中起着至关重要的作用,将先天免疫系统和适应性免疫系统联系在一起。

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