Halligan Doug N, Murphy Stephen J E, Taylor Cormac T
Conway Institute, Charles Institute & Systems Biology Ireland, University College Dublin, Belfield Dublin 4, Ireland; Sigmoid Pharma, Invent Centre, Dublin City University, Dublin 9, Ireland.
Conway Institute, Charles Institute & Systems Biology Ireland, University College Dublin, Belfield Dublin 4, Ireland.
Semin Immunol. 2016 Oct;28(5):469-477. doi: 10.1016/j.smim.2016.09.004. Epub 2016 Oct 4.
Crosstalk between metabolic and immune pathways has recently become appreciated to be key to the regulation of host defence. The hypoxia-inducible factor (HIF) is a transcription factor which was initially described as a ubiquitous master regulator of the transcriptional response to hypoxia. In this role, HIF regulates genes promoting adaptation to hypoxia including a number which influence the cellular metabolic strategy of a cell. It has more recently been appreciated that the regulation of HIF is not restricted to oxygen-dependent pathways, and is now known to be mediated by a number of additional metabolic and immune cues including metabolites and cytokines respectively. Furthermore, our understanding of the functional role of HIF has expanded to it now being appreciated as a major regulator of host immunity. This places HIF in an ideal position to act as a regulatory hub which links metabolic activity with immunity. In this review we synthesise recent data which identifies HIF as both a target and effector for metabolic and immune processes. Developing our understanding of the role of HIF in this context will uncover new therapeutic targets for inflammatory and infectious disease.
代谢途径与免疫途径之间的相互作用最近被认为是宿主防御调节的关键。缺氧诱导因子（HIF）是一种转录因子，最初被描述为对缺氧转录反应的普遍主调节器。在这一作用中，HIF调节促进适应缺氧的基因，包括一些影响细胞代谢策略的基因。最近人们认识到，HIF的调节不限于氧依赖途径，现在已知分别由包括代谢物和细胞因子在内的许多其他代谢和免疫信号介导。此外，我们对HIF功能作用的理解已经扩展，现在认为它是宿主免疫的主要调节器。这使HIF处于将代谢活动与免疫联系起来的理想调节枢纽位置。在这篇综述中，我们综合了最近的数据，这些数据将HIF确定为代谢和免疫过程的靶标和效应器。深入了解HIF在这种情况下的作用将为炎症和传染病发现新的治疗靶点。
