Edited by:
Dr. Peter Bunyard, PhD, Sitryx Therapeutics, United Kingdom
Dr. pharm. Marina Makrecka-Kuka, PhD, Sitryx Therapeutics, United Kingdom
Submission Status: Open | Submission Deadline: 6 January 2025
Journal of Inflammation is calling for submissions to our Collection on From theory to therapy; understanding and targeting immunometabolism for the treatment of inflammation and cancer. Metabolism describes the fundamental life sustaining process whereby living organisms catalyze both simple and complex chemical compounds such as salts, glucose and amino acids to derive energy and the building materials necessary to support growth, reproduction, communication and motility. Immunometabolism: the study of the metabolic processes that support immunity has long been at the cutting edge of immunology research given the importance of metabolism in maintaining health and driving disease. Cellular metabolism affects all aspects of immune function from homeostasis to cell activation with cell division and cell differentiation being notable examples. Further immune mechanisms such as antibody isotype switching; cytokine production; chemotaxis and phagocytosis are also governed in large part through metabolic processes.
Since the 1950’s drugs that target key enzymes in metabolic pathways have been used to treat auto-immune conditions such as rheumatoid arthritis and Inflammatory Bowel Disease. Examples include methotrexate and 5-fluorouracil that primarily inhibit dihydrofolate reductase and thymidylate synthase respectively. These enzymes that play important roles in the 1-carbon metabolism pathway producing purines and pyrimidines for RNA and DNA synthesis required for cell growth and proliferation. Despite the success of these compounds significant issues remain, most notably challenging side-effect profiles caused by the fundamental role that these enzymes play in numerous biological processes beyond those driving disease; these side effects limit the tolerability and effectiveness of such therapies.
Advances in molecular biology techniques such as CRISPR and knockout mice have provided new insights over the role that various enzymes play in metabolic pathways and have demonstrated that immune cells can utilize various metabolic pathways differently from surrounding homeostatic processes allowing more targeted therapy. Recent work by Jefff Rathmell et al., demonstrated that Th1 and Th17 helper T-ells are more dependent on the 1-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) than the majority of cells in the body: expression is also strongly upregulated upon activation and proliferation. Selective inhibition of MTHFD2 therefore holds the promise of being able to more specifically reduce inflammation without the debilitating side effects of methotrexate.
Beyond autoimmunity, immunometabolism may also play important roles in oncology and diet driven inflammation. For example, obeticholic acid has demonstrated efficacy in animal models of non-alcoholic steatohepatitis through modulating the farnesoid X receptor and subsequently inhibiting hepatic gluconeogenesis and fatty acid synthesis. The tumor micro-environment has also been shown to be devoid of numerous metabolites required to maintain the function of tumor killing CD8+ T-cells and also contains metabolites that can enhance T-reg immune tolerance.
Given the fundamental role for metabolism in the immune system, the knowledge that existing therapies modulate immune metabolism and that numerous targetable enzymes, transporters and receptors exist - immunometabolism remains at the forefront of medicinal research and drug discovery. However new insights that demonstrate the role of immunometabolism in basic and clinical research and highlight the importance of key molecules in metabolism pathways are urgently required. In this regard, we welcome original research articles (including preclinical and clinical trials, epidemiological studies, and case studies), comprehensive reviews, meta-analysis reports, and commentaries.
Potential topics include but not limited to:
1. Defined roles for metabolic pathways or metabolites in immune cell function related to homeostasis inflammation or immune-oncology.
2. Rationale and evidence for new pharmacological targets for the treatment of disease.
3. Impact of aging on immunometabolism and immune cell function.
4. Links between nutrition, metabolic pathways and immune cell function in health and disease.
5. Association studies linking therapies that target metabolism to immune cell function.
Image credits: Peter Bunyard (Created with BioRender.com)
This collection supports and amplifies research related to SDG 3: Good health and well-being.