The cellular nutrient glutamine launches a metabolic signaling pathway that promotes the function of some immune system T cells and suppresses others, Vanderbilt researchers have discovered.
They show that a drug that inhibits glutamine metabolism — currently in clinical trials as an anticancer agent — might also be useful as a treatment for inflammatory and autoimmune diseases. The study, published online this week in the journal Cell, also suggests strategies for using the drug to enhance cancer immunotherapies.
Jeffrey Rathmell, PhD, Cornelius Vanderbilt Professor of Immunobiology, and his colleagues have focused on trying to understand how a cell integrates its nutrients and metabolism with its function. They previously demonstrated the importance of the cellular fuel glucose for the activation and function of T cells that drive inflammation and eliminate pathogens.
In the current work, they turned their attention to another major fuel: glutamine, which has primarily been studied in the context of cancer cell metabolism. Several companies are developing drugs that inhibit glutamine metabolism to reduce cancer cell growth and proliferation.
The investigators expected that inhibiting glutamine metabolism — like blocking glucose metabolism — would prevent T cell activation and function. They used a drug that inhibits the first