Thomas Riffelmacher, Ph.D.

Are fat-addicted MAIT cells driving liver disease?

Fatty liver disease is the most common chronic liver disorder, affecting 25 percent of Americans. It is a progressive yet silent disease that stays asymptomatic in earlier stages. On the molecular level, we know an effector molecule called IL-17 drives disease, but we don’t know why the disease rapidly progresses in some individuals while others remain healthy.

My previous research has focused on an immune cell called the MAIT cell (in the lungs) that is good at producing IL-17. This type of cell is fueled by fat. When we remove fat as a nutrient source, or target MAIT cell lipid metabolism pharmacologically, they stop making IL-17. MAIT cells are highly enriched in the liver. So, I believe MAIT-cell-derived IL-17 may be the key driver of fatty liver disease in progressive patients.

Using human samples, I will isolate the MAIT cells and perform metabolomic analysis via mass-spectrometry. This state-of-the-art technology will allow me to study the metabolic wiring of cells in great detail. Together with immune assays of effector molecules, this will give us a detailed picture of the link between fat metabolism and the immune effect of MAIT cells in liver disease. If my hypothesis turns out to be correct, we can design future treatments to target these cells.

SPARKing Impact: Fatty liver disease affects one quarter of Americans. I believe targeting MAIT cell subsets that thrive in the fatty liver environment can stop disease progression. My project aims to provide proof-of-concept that these cells become addicted to fat and drive disease.