Review Article | Published:

Metabolic regulation of inflammation

Nature Reviews Rheumatology volume 13, pages 267279 (2017) | Download Citation

Abstract

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Key points

  • Immune cells face a variety of variable and sometimes demanding environmental conditions, requiring them to display a dynamic range of metabolic adaptation processes

  • Under inflammatory conditions, stimulated immune cells have an acute need to generate sufficient energy and biomolecules to support growth, proliferation and the production of proinflammatory molecules

  • Metabolic reconfiguration varies between innate and adaptive immune responses, and influences both the effector phase of inflammation and the resolution of inflammation by modulating immune cell fate and function

  • Metabolic enzymes, metabolites and regulators of metabolism have a direct influence on certain inflammatory responses

  • Alterations of metabolic configurations of immune cells can contribute to dysfunctional immune responses, a typical feature of autoimmunity

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Affiliations

  1. Charité University Hospital, Department of Rheumatology and Clinical Immunology, Charité University Medicine, Charitéplatz 1, 10117 Berlin, Germany.

    • Timo Gaber
    • , Cindy Strehl
    •  & Frank Buttgereit
  2. German Rheumatism Research Centre (DRFZ), Charitéplatz 1, 10117 Berlin, Germany.

    • Timo Gaber
    • , Cindy Strehl
    •  & Frank Buttgereit

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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to Frank Buttgereit.

Glossary

Glycolysis

An oxygen-independent metabolic pathway that generates two molecules of pyruvate, ATP and NADH from every one molecule of glucose, supporting the tricarboxylic acid cycle and providing intermediates for the pentose phosphate pathway, glycosylation reactions and the synthesis of biomolecules (including serine, glycine, alanine and acetyl-CoA)

Tricarboxylic acid (TCA) cycle

(Also known as the Krebs cycle) A set of connected pathways in the mitochondrial matrix, which metabolize acetyl-CoA derived from glycolysis or fatty acid oxidation, producing NADH and FADH2 for the electron transport chain and precursors for amino acid and fatty acid synthesis

Electron transport chain

A series of proteins in the inner mitochondrial membrane that transfer electrons from one to the other in a series of redox reactions, resulting in the synthesis of ATP and in the movement of protons out of the mitochondrial matrix

Oxidative phosphorylation

A metabolic pathway that produces ATP from the oxidation of acetyl-CoA and the transfer of electrons to the electron transport chain via NADH and FADH2

Fatty acid oxidation

A metabolic process that produces ATP from the oxidation of acetyl-CoA derived from the mobilization of fatty acids

Glutaminolysis

The metabolic process by which glutamine is metabolized to glutamate and then to α-ketoglutarate to replenish the tricarboxylic acid cycle

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https://doi.org/10.1038/nrrheum.2017.37

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