Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Front Immunol. 2021 Oct 25:12:748573. doi: 10.3389/fimmu.2021.748573. eCollection 2021.

Abstract

The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.

Keywords: cytokine storm; immunometabolic reprogramming; inflammatory diseases; proinflammatory cytokines; pyruvate kinase M2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Carrier Proteins / agonists
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / chemistry
  • Carrier Proteins / physiology*
  • Cell Nucleus / enzymology
  • Cytokine Release Syndrome / enzymology*
  • Cytokines / metabolism
  • Dendritic Cells / enzymology
  • Enzyme Activation
  • Ferroptosis
  • Glycolysis
  • Humans
  • Inflammasomes
  • Inflammation
  • Killer Cells, Natural / enzymology
  • Macrophages / enzymology
  • Membrane Proteins / agonists
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology*
  • Molecular Structure
  • Oxidation-Reduction
  • Protein Conformation
  • Pyroptosis
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / agonists
  • Thyroid Hormones / chemistry
  • Thyroid Hormones / physiology*

Substances

  • Carrier Proteins
  • Cytokines
  • Inflammasomes
  • Membrane Proteins
  • Thyroid Hormones