Study decodes connection between metabolism and immunity in genetic diseases

Researchers have decoded the connection between metabolism and immunity in inherited diseases.

Researchers from the Vanderbilt University Medical Center in the US identified a new set of metabolic genes crucial for T cell function, offering potential improvements in the treatment of patients with these disorders.

The team focussed on genes responsible for inborn errors of metabolism -- disorders affecting cellular energy conversion -- and inborn errors of immunity, which impact immune system function. These rare diseases are complex and not fully understood.

"Previously, only a small number of genes were determined to be associated with both lists of disorders; however, we discovered that many more genes share similarities," said Andrew Patterson, PhD, who led the study at Vanderbilt. The research revealed that a significant number of genes associated with metabolic disorders also affect T-cell function when mutated.

These findings suggest that patients with metabolic disorders may have underlying immune defects that could influence their care, and conversely, metabolic defects may contribute to symptoms in patients with immune system disorders.

"Though much more research is needed, these linkages may suggest other treatment approaches," said Jeffrey Rathmell, director of the Vanderbilt Center for Immunobiology.

He added that rather than being separate categories, these diseases exist on a continuum, with a potential new class of inborn errors of immunometabolism that intersects the two.

The research team used CRISPR gene-editing technology to screen genes associated with metabolic disorders for immune defects and vice versa. They then closely examined one gene from each category to understand its impact on T cell function.

The team aims to uncover how metabolic pathways regulate T-cell function to develop 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 analyse for their roles in T cell function."