A newly found metabolism and immunity link offers insights into rare disease management
Why this matters: the study adds to a growing view that immune cells are not just regulated by genes and signals, but also by the metabolic pathways that supply them with energy and building blocks. That helps explain why some inherited metabolic disorders may have immune features that are easy to miss in routine care.
Important caveat: the findings come from a CRISPR screening approach in CD4 T cells, which is powerful for mapping biology but not the same as studying a patientโs day-to-day disease course. A gene knockout can reveal what a pathway can do, yet many real-world mutations are partial, tissue-specific, or compensated for by other pathways. So the work is best read as a mechanistic map, not a direct clinical test.
Practical implication: the most immediate value may be diagnostic rather than therapeutic. In complex rare diseases, immune dysfunction can be overshadowed by neurological, muscular, or systemic symptoms. This research supports a broader checklist for clinicians and specialists: if a metabolic disorder looks unusually inflammatory, infection-prone, or autoimmune, the immune system may deserve separate evaluation.
Broader context: the same biology cuts both ways. T cells need flexible metabolism to work properly, but that also means changing their metabolic environment could potentially strengthen anti-tumor responses or dampen autoimmunity. That idea is plausible and exciting, yet still early-stage. For readers, the key takeaway is that metabolism and immunity are increasingly being understood as intertwined systems, not separate silos.
Every part of the body has its own microenvironment with different nutrient availability.Immunometabolism and precision medication
Theย studyย published inย Science Immunologyย discusses the concept of immunometabolism. Concerning how he sees the concept evolving and what impact it could have on the future of precision medicine, Patterson says that โimmune cells are wonderfully dynamic.โ โThey have to be able to adapt to a wide range of different stimuli and microenvironments. A T cell can hang around in your body for years, remaining relatively quiescent with low metabolic requirements, just waiting to see its specific target (cognate antigen). When it finally does, the cell must not only rapidly grow and divide, but also differentiate to be a better responder to its target,โ he explains. โThese changes require both energy and nutrient building blocks to help generate all the cellular machinery and structures the cell needs to function. Furthermore, the immune cell must migrate to the region of the body where it’s needed.โ โHowever, every part of the body has its own microenvironment with different nutrient availability (what the nutrient cell has available in the intestines is not necessarily the same as what is available in the liver or skin).โ He says that an immune cell in that microenvironment has to adapt its metabolism to that microenvironment or it may lose its functionality, adding that this is one of the reasons why immune cells attacking tumors don’t always do well. โTrying to tweak the metabolism of immune cells based on their microenvironment is an exciting possibility to improve their function in cases like cancer or to tamp down their inflammatory ability in the context of autoimmunity.โCRISPR gene-editing approach
Patterson and his team used a gene-editing CRISPR approach to screen the inborn errors of metabolism genes for immune defects and the inborn errors of immunity genes for metabolic defects. They analyzed one example from each set, including one metabolic gene with an immune defect and one immunity gene that had a metabolic defect, in order to more carefully examine the mechanistic impact. โThe study was built on a pooled CRISPR screening approach, in which we used CRISPR to knock out our genes of interest (those associated with the Inborn Errors) and then evaluate the broad effects of the loss of that gene in CD4 T cells. While we expected several genes to be identified in this study, it was a bit surprising how much overlap we found,โ he tells us. Patterson states that his teamโs findings could be translated into potential therapies in the future.โWe also used CRISPR to specifically knock out Gfpt1 in further environments. While most of the work we did with CRISPR was straightforward, the challenges lay with the caveats of the technology we used. T cells are notoriously difficult to generically manipulate, so we had to perform CRISPR in cells that had already been activated.โ โThe CRISPR strategy we used also results in a full loss of protein, whereas mutations that cause the Inborn Errors of Immunity and Metabolism may cause partial or abnormal protein function. So while our approach is good for identifying immunometabolic regulators, it does not test all the specific mutations found in the Inborn Errors disorders.โFuture implications
Patterson states that his teamโs findings can be translated into potential therapies, while acknowledging that โfor the moment, this work is still very much on the basic sciences side of research.โ โHowever, we hope by identifying new metabolic regulators of the immune system, targeted therapies could be used to โfine tuneโ in immune responses in the context of autoimmunity, cancer or infection.โ Regarding the next steps for the research team in exploring the identified genes, Patteson points the lab he recently started as an assistant professor of biochemistry and molecular genetics at the University of Louisville, US where he will continue to investigate the genes identified as immunometabolic regulators. โWe also developed anย online databaseย (the Functional ImmunoGenomics reSource) to share our CRISPR screening results so that other groups can use this data to further their own research.Enjoyed this article? Sign up for our newsletter to receive regular insights and stay connected.