How immune cell networks drive liver disease

A type of rare T cell triggers a cascade of signals amplifying inflammation and ultimately leading to liver fibrosis, according to a new study from Julius Maximilian University of Würzburg published in Nature Communications. Over time, this process contributes to a sustained decline in liver function.

When the liver is injured—for example, due to bile accumulation—immune cells become activated. In mouse experiments, the Würzburg team observed that certain immune cells undergo functional changes in response to liver damage, adopting a highly pro-inflammatory state. Using advanced single-cell sequencing and high-resolution spatial analysis, the researchers identified a direct interaction between two types of immune cells: dendritic cells and a specific subset of rare T cells known as γδ T cells.

The identified cell types communicate through direct contact, triggering the release of the pro-inflammatory signaling molecule interleukin-17. This process plays a key role in driving both liver inflammation and fibrosis. Dr. Dr. Stefan Thomann, first author of the study and a postdoctoral researcher in Dominic Grün’s lab, explains. “We found that removing specific immune cell populations significantly reduces both inflammation and scarring. This suggests that their interaction is a critical driver of disease progression.”

Importantly, these mechanisms were confirmed in human tissue samples. “We hope that, in the long term, our findings will help pave the way for more targeted therapies to slow the early development of liver disease,” says Professor Grün, Chair of Computational Biology of Spatial Biomedical Systems and Director at the Institute of Systems Immunology at the University of Würzburg.

Before these insights can be translated into clinical therapies, the underlying mechanisms need to be investigated in greater detail and validated in further human studies. In parallel, the research team is now exploring whether similar processes occur across different liver diseases, including common conditions such as metabolic dysfunction-associated fatty liver disease.