Inherited metabolic and immune disorders share more similarities than previously thought, as revealed by a recent study. This research highlights a new group of metabolic genes crucial for the functioning of T cells in the immune system and suggests ways to enhance treatment for patients with these conditions.
Inherited metabolic and immune disorders have more in common than previously recognized, according to a recent study published in Science Immunology. The research identifies a new collection of metabolic genes that play a significant role in T cell function within the immune system, providing potential strategies to enhance patient care for those with these disorders.
The study explored genes responsible for inborn errors of metabolism—issues related to how cells convert food into energy—and inborn errors of immunity that interfere with the immune system. These rare and intricate diseases remain partially understood.
“Previously, only a handful of genes were recognized in both categories of diseases, but we discovered a greater overlap,” stated Andrew Patterson, PhD, the lead researcher and former postdoctoral fellow at Vanderbilt University Medical Center. “Our work indicated that numerous genes linked to inborn metabolism errors could also potentially impact T cell functionality if mutated.”
This research implies that individuals with metabolic disorders might also experience immune deficiencies that affect their healthcare, and that metabolic issues could exacerbate symptoms in those with immune disorders.
“There’s still much to learn, but these findings could lead to new treatment options,” said Rathmell, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “Instead of viewing these conditions as separate, they may represent a continuum; there are overlaps creating a potential new category of inborn errors of immunometabolism that blends the two.”
Patterson and his team utilized a CRISPR gene-editing technique to examine metabolic genes for immune deficiencies and immune genes for metabolic problems. They analyzed one gene from each category—a metabolic gene exhibiting an immune defect and an immunity gene showing a metabolic defect—to delve deeper into the underlying mechanisms.
Overall, Rathmell’s research group is focused on uncovering how metabolic pathways influence T cell activity in hopes of developing specific therapies for disorders driven by immune responses.
“What we have established is the groundwork for future research,” Patterson explained. “The two examples we investigated in detail introduce new biological insights and mechanisms, plus we identified hundreds of other genes that need to be examined for their role in T cell functionality.”
The results are accessible on the Functional ImmunoGenomics reSource (FIGS) website, available for other researchers to utilize.
“If you’re looking to explore the links between metabolism and immunity, this resource is an excellent starting point,” Rathmell noted.
Patterson has recently joined the University of Louisville as an assistant professor in Biochemistry and Molecular Genetics. Collaborators from Vanderbilt, including Vivian Gama, PhD, an associate professor of Cell and Developmental Biology, and Janet Markle, PhD, an assistant professor of Pathology, Microbiology, and Immunology, were key contributors to the research.
