Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
HIF1α and metabolic reprogramming in inflammation
Sarah E. Corcoran, Luke A.J. O’Neill
Sarah E. Corcoran, Luke A.J. O’Neill
Published August 29, 2016
Citation Information: J Clin Invest. 2016;126(10):3699-3707. https://doi.org/10.1172/JCI84431.
View: Text | PDF
Review Series

HIF1α and metabolic reprogramming in inflammation

  • Text
  • PDF
Abstract

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.

Authors

Sarah E. Corcoran, Luke A.J. O’Neill

×

Figure 2

HIF1α and the Th17/Treg axis.

Options: View larger image (or click on image) Download as PowerPoint
HIF1α and the Th17/Treg axis.
HIF1α plays a role in T cell differentiati...
HIF1α plays a role in T cell differentiation. HIF1α directly activates RORγt transcription and is also involved in the regulation of IL-17 production through association with RORγt and recruitment of p300 at the IL17A promoter. HIF1α also impedes Treg differentiation by directly binding FOXP3, promoting its proteasomal degradation. Inhibition of glycolysis by 2-DG leads to an oxidative Treg phenotype (22, 72).
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts