[HTML][HTML] HIF1α and metabolic reprogramming in inflammation

SE Corcoran, LAJ O'Neill - The Journal of clinical …, 2016 - Am Soc Clin Investig
SE Corcoran, LAJ O'Neill
The Journal of clinical investigation, 2016Am Soc Clin Investig
HIF1α is a common component of pathways involved in the control of cellular metabolism
and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for
the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-
activated macrophages, where it is critically involved in glycolysis and the induction of
proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction
involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) is …
HIF1α is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) is also induced and interacts with and promotes the function of HIF1α. In another critical inflammatory cell type, Th17 cells, HIF1α acts via the retinoic acid–related orphan receptor-γt (RORγt) to drive Th17 differentiation. HIF1α is therefore a key reprogrammer of metabolism in inflammatory cells that promotes inflammatory gene expression.
The Journal of Clinical Investigation