Research Topic

Role of Metabolism in Regulating Immune Cell Fate Decisions

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Cellular metabolism encompasses catabolic and anabolic pathways to generate and use energy in the form of ATP to support survival and to produce numerous biosynthetic precursors for cellular growth and proliferation. In the last decade, the immunology field has seen a tremendous increase in research interest ...

Cellular metabolism encompasses catabolic and anabolic pathways to generate and use energy in the form of ATP to support survival and to produce numerous biosynthetic precursors for cellular growth and proliferation. In the last decade, the immunology field has seen a tremendous increase in research interest on how metabolic alterations that occur during immune cell activation influence immune cell differentiation and function. As an example, the activation of macrophages with proinflammatory (M1) stimuli induces metabolic reprograming away from the mitochondrial oxidative phosphorylation to aerobic glycolysis and increased activity via the pentose phosphate pathway. In M1 macrophages, the tricarboxylic acid (TCA) cycle is broken and reconfigured from a catabolic pathway to a partly anabolic system. These complex metabolic changes are required for the generation of redox equivalents and precursor molecules (amino acids, lipids, nucleotides) to drive proinflammatory mediator production (cytokines, reactive oxygen species and nitric oxide). In contrast, anti-inflammatory M2 macrophages have an intact TCA cycle and use oxidative phosphorylation, fatty acid oxidation and arginase-mediated arginine metabolism to support longevity and M2 functions.

Similarly, metabolic fluxes during T cell activation and differentiation are well studied: rapidly proliferating effector T cells (Th1, Th17 and cytotoxic CD8+ T cells) utilize aerobic glycolysis, fatty acid synthesis and amino acid metabolism to promote cell proliferation and cytokine secretion, while the metabolic switch to fatty acid oxidation and oxidative phosphorylation is required to generate memory as well as regulatory T cells.

Additionally, metabolites can be released into extracellular space to promote intercellular communication. Activated immune cells (e.g. T cells, macrophages and others) release ATP to support cell migration or activation (to sustain calcium flux or activate NLRP3 inflammasome-dependent IL-1β maturation). During the resolution of inflammation, extracellular ATP is metabolized to adenosine that promotes M2 macrophage polarization and regulatory T cell generation. Similarly, lactate accumulated during aerobic glycolysis of macrophages, T cells as well as cancer cells potently inhibits T and NK cell responses. However, in general, the role of metabolism in regulating cell fate of other immune cells is less well understood than of macrophages and T cells.

This Research Topic aims to provide a comparative overview of the role of metabolism in regulating cell fate decisions in different immune cell types. We welcome high quality Original Research, Review, Mini-Review and Perspective articles that aim to either:

(i) Provide a mechanistic insight into activation-mediated metabolic changes in immune cells (macrophages, dendritic cells, granulocytes, mast cells, T cells, B cells, NK cells and other innate lymphocytes), and subsequent effects onto cell fate decisions in these cell types, or
(ii) Report on altered immune cell metabolism in pathologic states.

The goal is to bring together immunologists from different areas, clinicians and biochemists, and identify common pathways and mechanisms that may be important in multiple cell types and on the other hand, pinpoint the immune-cell-specific mechanisms in order to provide novel understanding of immunometabolism in health and disease (infection, autoimmunity and cancer).

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.


Keywords: immunometabolism, metabolic reprogramming, immune cell regulation


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