New Study Exposes Connections Between Metabolism and Immunity

A recent study published in Science Immunology reveals significant genetic overlap between inherited metabolic and immune disorders, pointing to a new set of metabolic genes that are important for the function of T cells.

The study, led by Andrew Patterson during his postdoctoral work at Vanderbilt University Medical Center, explored genes responsible for inborn errors of metabolism and immunity. These rare disorders, involving cellular energy conversion and immune function, respectively, were found to have more genetic overlap than previously recognized.

Patterson noted, "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 indicate that patients with metabolic disorders might also experience immune defects, and vice versa, suggesting new therapeutic approaches. Jeffrey Rathmell, the study's senior author, emphasized, "Rather than different categories, these diseases are part of a continuum; there’s a gray zone between them."

Using CRISPR gene-editing technology, the researchers screened genes associated with metabolic and immune defects. They analyzed specific genes from each category to understand their mechanistic impacts on T cell function. This work lays the groundwork for future investigations into how metabolic pathways regulate immune responses, with the aim 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.” 

The findings are available on FIGS (Functional ImmunoGenomics Resource) for other researchers to use. 

“If you’re trying to understand the connections between metabolism and immunity, this is a great place to start,” Rathmell said.