HIF1α and metabolic reprogramming in inflammation

HIF1 alpha is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1 alpha is critical for the maturation of dendritic cells and for the activation of T cells. HIF1 alpha is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably II1b. The mechanism of LPS-stimulated HIF1 alpha induction involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) is also induced and interacts with and promotes the function of HIF1 alpha. In another critical inflammatory cell type, Th17 cells, HIF1 alpha acts via the retinoic acid-related orphan receptor-gamma t (ROR gamma t) to drive Th17 differentiation. HIF1 alpha is therefore a key reprogrammer of metabolism in inflammatory cells that promotes inflammatory gene expression.