How Immune Cell Networks Drive Liver Disease

Researchers at Julius Maximilian University of Würzburg have gained new insights into how liver diseases develop. In a study published in the scientific journal Nature Communications, the team led by Dominic Grün reveals which immune responses in the liver initiate tissue damage - and highlights potential targets for future therapies aimed at slowing the onset and progression of liver disease.

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.

These cells communicate with other immune cells, triggering a cascade of signals that amplify inflammation and can ultimately lead to liver fibrosis. Over time, this process contributes to a sustained decline in liver function.

Mitigating Liver Inflammation and Fibrosis

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 not only observed in mice but were also 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 Dominic 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.
 

Original publication: www.nature.com

Figure: The immunobiliary niche in the mouse liver under healthy conditions and during bile retention. Immunofluorescence staining illustrates tissue changes associated with the DDC diet, which was used by the researchers to investigate the cellular composition and interactions of immune cells at the bile ducts in the liver. With increasing duration of bile retention, pro-inflammatory immune cells are recruited, promoting liver fibrosis. Even in healthy liver tissue, immune cells (CD45) can be observed in direct contact with bile ducts (Epcam).

Abbreviations: A, hepatic artery; BD, bile duct; ly, lymphatics; PV, portal vein.

Copyright: Julius-Maximilians-Universität Würzburg / Stefan Thomann

Kontakt
Dr. Dr. Stefan Thomann
stefan.thomann@uni-wuerzburg.de

Prof. Dr. Dominic Grün
dominic.gruen@uni-wuerzburg.de
Grün Lab

Public Relations
Christina Bornschein
christina.bornschein@uni-wuerzburg.de