title: The hypoxia-inducible factor (HIF) couples immunity with metabolism.
abstract: 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.
authors.affiliation: Conway Institute, Charles Institute & Systems Biology Ireland, University College Dublin, Belfield Dublin 4, Ireland; Sigmoid Pharma, Invent Centre, Dublin City University, Dublin 9, Ireland.
authors.forename: Doug N
authors.initials: DN
authors.lastname: Halligan
authors.affiliation: Conway Institute, Charles Institute & Systems Biology Ireland, University College Dublin, Belfield Dublin 4, Ireland.
authors.forename: Stephen J E
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Conway Institute, Charles Institute & Systems Biology Ireland, University College Dublin, Belfield Dublin 4, Ireland; IRCAN, Centre A. Lacassagne, University of Nice-Sophia Antipolis, 33 Avenue Valombrose, 06107 Nice, France; Centre Scientifique de Monaco (CSM), 8, Quai Antoine Premier, Monaco. Electronic address: cormac.taylor@ucd.ie.
authors.forename: Cormac T
authors.initials: CT
authors.lastname: Taylor
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007109:Immunity; D056747:Immunomodulation; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051793:Hypoxia-Inducible Factor 1; D006899:Mixed Function Oxygenases
keywords: Hypoxia; Immunometabolism; Immunometabolite; Mitochondria; Therapeutics