Dubai: Inherited diseases of metabolism and immunity have more in common than previously recognised, according to a new study published in the journal Science Immunology.
The findings point to a new set of metabolic genes that are important for the function of immune system T cells, and they offer insights that could improve care for patients with these disorders.
The results provide fresh information that may help patients with these illnesses receive better care by highlighting a novel collection of metabolic genes that are critical for immune system T cell activity.
The findings of the study were published in the journal Science Immunology.
The study looked at the genes that lead to inborn errors of immunity, which are illnesses that impact immune system function, and inborn errors of metabolism, which are diseases of the mechanisms cells employ to transform food into energy. We don’t fully understand these uncommon and complicated disorders.
“There had previously been only a small number of genes that were on both lists of diseases, but we found that many more have overlap,” said Dr Andrew Patterson who led the study as a postdoctoral fellow working with Dr Jeffrey Inborn errors
Rathmell at Vanderbilt University Medical Centre, Nashville. “Our study showed that a large number of genes associated with inborn errors of metabolism can also potentially affect T cell function when they are mutated.”
The findings suggest that patients with an inborn error of metabolism may also have immune defects that could impact their care, and conversely that metabolic defects may contribute to symptoms in patients with inborn errors of immunity.
“There’s a lot more that will have to be learned, but these connections might point to different therapies,” said Rathmell, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Centre for Immunobiology. “Rather than different categories, these diseases are part of a continuum; there’s a gray zone between them and a potential new class of inborn errors of immunometabolism that intersects the two.”
Gene-editing
Patterson and the research 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 further analyzed one example from each set — one metabolic gene that had an immune defect; one immunity gene that had a metabolic defect —to more carefully examine the mechanistic impact.
Overall, Rathmell’s team is interested in discovering how metabolic pathways regulate T cell function, with the goal of developing targeted therapies for immune-mediated disorders.
“What we’ve done is lay the foundation for further investigation,” Patterson said. “The two examples we studied in detail point to new biology and new mechanisms, and there are hundreds of other genes we identified to analyze for their roles in T cell function.”
“If you’re trying to understand the connections between metabolism and immunity, this is a great place to start,” Rathmell said.
Patterson recently joined the faculty of the University of Louisville as an assistant professor of Biochemistry and Molecular Genetics. Vanderbilt collaborators Dr Vivian Gama, associate professor of Cell and Developmental Biology, and Dr Janet Markle, assistant professor of Pathology, Microbiology and Immunology, were important contributors to the study.
