Hypoxia-inducible factors: key regulators of myeloid cells during inflammation

Regulation of immunity and inflammation by hypoxia in immunological niches

“…The specific functions of HIF in individual immune cell types has been recently reviewed and will be discussed only briefly here (reviewed in REFS 11,12). In neutrophils, HIF has a key role in the regulation of lifespan, antimicrobial peptide production and apoptosis 47,48 . By contrast, in macrophages, HIF regulates M1 and M2 polarization, motility, bactericidal activity and tumour development 48,49 .…”

“…In neutrophils, HIF has a key role in the regulation of lifespan, antimicrobial peptide production and apoptosis 47,48 . By contrast, in macrophages, HIF regulates M1 and M2 polarization, motility, bactericidal activity and tumour development 48,49 . In dendritic cells (DCs), HIF modulates survival, migration, antigen presentation, interferon synthesis and differentiation 50,51 .…”

Detection of Hypoxia and HIF in Paraffin-Embedded Tumor Tissues

“…Therefore, maintenance of O 2 homeostasis is critical for the survival of most prokaryotic and eukaryotic species [1,2]. O 2 deprivation (hypoxia) triggers complex adaptive responses to match O 2 supply with metabolic and bioenergetic demands.…”

“…When faced with hypoxia, mammalian cells engage multiple evolutionarily conserved molecular responses, including those coordinated by the hypoxia-inducible factors (HIF) transcriptional regulators. Under normoxic conditions, HIFs are rapidly degraded through an ubiquitin-proteasome pathway, whereas hypoxia results in the stabilization and nuclear translocation of HIF[1,2]. HIFs, including HIF1α and HIF2α, transactivate a wide range of genes involved in the regulation of angiogenesis, metabolism, cell survival, and inflammation [3].…”

Mesangial renal disease, oxygen sensing, and prolyl hydroxylase

“…Hypoxia stabilizes HIFs in macrophages and neutrophils and thus serves to regulate inflammatory responses in myeloid cells. Thereby, HIF could shape macrophage and neutrophil function in mediating inflammatory disease [10]. Other HIF stabilization-driven functions in gene expression could influence perfusion and endothelial function, reprogram metabolism to promote glucose intake and glycolysis over oxidative metabolism, reduce inflammation, and beneficially modify the innate immune system [11].…”