About this Research Topic
Cellular metabolism is the umbrella term used to describe how cells generate the energy and metabolites required for cell growth and maintenance. Immunometabolism then refers to the central role that metabolism plays in shaping the development, differentiation, and function of immune cells. At its core is the premise that the engagement of specific metabolic pathways, the production or utilization of specific metabolites, or the non-canonical functions of metabolic enzymes can be decisive in the balance between inflammation, tolerance, or resolution.
Examples of this are highlighted in the innate immune system, where macrophages exposed to the bacterial product lipopolysaccharide and the cytokine interferon-gamma exhibit significant alterations in glycolysis and the tricarboxylic acid cycle that result in the accumulation of metabolites required to drive and regulate the production of inflammatory cytokines. This stands in contrast to macrophages with pro-resolving and wound healing functions that instead require intact mitochondrial respiration and fatty acid oxidation for optimal function. In the adaptive immune system, cellular metabolism is also crucial for facilitating the differentiation and effector responses of both CD4+ and CD8+ T cells and in controlling populations of long-lived memory cells through its effects on RNA translation and epigenetic regulation among others.
The metabolic phenotype of immune cells can be modulated by the environment they find themselves present within. For example, recent studies show that skin-resident memory T cells acquire fatty acids from their environment and increase mitochondrial activity, which are required for their longevity and capacity to provide protective immunity within this niche unlike central memory T cells, which convert glucose into fatty acids for subsequent oxidation. Research into the tumor microenvironment demonstrates a competition for nutrients between cancer and immune cells that can impact the ability of the immune system to control or eliminate tumors. However, how different complex tissue microenvironments mold the cellular metabolism of resident immune cells either in physiological or diseased settings is still not well understood. Furthermore, how the tissue context-specific metabolic activity tailors immune responses in resident immune cells remains unexplored.
In vitro studies have been essential in elucidating findings that have helped establish the immunometabolism field. Metabolic analyses often require cell numbers and interventions only feasibly achieved in vitro, however, whether these data faithfully translate to bona fide tissue-resident immune cells in vivo has sometimes been questioned. To address this issue, there have been calls to utilize ‘physiological mediums’ with metabolite compositions based on human or mouse plasma serum concentrations to refine in vitro culture. Additionally, metabolomics methodologies continue to advance with different research groups attempting to dissect the metabolic profiles of immune cells as they are in situ.
This Research Topic aims to enhance the state of knowledge pertaining to tissue-resident immune cell metabolism and how cellular immunometabolism relates to tissue functions. We welcome high-quality Original Research, Mini Review, Review, and Perspective articles that aim to:
1. Report on observations of immune cell metabolism within tissues and its impact on immunity.
2. Provide mechanistic understanding into how the tissue microenvironment shapes the cellular metabolism of immune cells.
3. Offer insight into how immune cell metabolism supports tissue homeostasis.
Studies focusing purely on Immunometabolism without connection to tissue homeostasis, or the role of tissues in shaping immune cell metabolism, will be deemed out of scope.
Dr. Ho receives financial support from Roche. The other Topic Editors declare no competing interests with regards to the Research Topic theme.
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