Key Points
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Immune cells face a variety of variable and sometimes demanding environmental conditions, requiring them to display a dynamic range of metabolic adaptation processes
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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
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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
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Metabolic enzymes, metabolites and regulators of metabolism have a direct influence on certain inflammatory responses
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Alterations of metabolic configurations of immune cells can contribute to dysfunctional immune responses, a typical feature of autoimmunity
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.
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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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Gaber, T., Strehl, C. & Buttgereit, F. Metabolic regulation of inflammation. Nat Rev Rheumatol 13, 267–279 (2017). https://doi.org/10.1038/nrrheum.2017.37
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DOI: https://doi.org/10.1038/nrrheum.2017.37
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MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria
Stem Cell Research & Therapy (2024)
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JAK1/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia
Journal of Neuroimmune Pharmacology (2024)
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PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy
Journal of Molecular Medicine (2024)
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Multimodal positron emission tomography (PET) imaging in non-oncologic musculoskeletal radiology
Skeletal Radiology (2024)