Understanding liver fibrosis: Insights from Alagille syndrome

What influences the extent of scar tissue, or fibrosis, that develops in the liver when people suffer from liver disease? While a small amount of fibrosis is a normal part of the healing process, excessive fibrosis can occur, leading to complications and, ultimately, liver failure. Understanding the mechanisms that drive this escalation is essential in the fight against liver disease.

To answer this, researchers from Karolinska Institutet and Charles University studied a genetic disease called Alagille syndrome, which is characterized by surprisingly mild liver fibrosis despite severe liver disease (pericellular fibrosis instead of bridging).

By employing single-cell RNA sequencing and transplanting immune cells from the mouse model into a different model of liver disease, the team uncovered that the immune system in patients with Alagille syndrome plays a role in suppressing scar tissue formation in the liver.

“We believe these findings could have broader implications for treating liver fibrosis, potentially through targeted manipulation of the immune system,” say Emma Andersson and Jan Mašek who led the team of international researcher collaborators.

The paper is published in the journal EMBO Molecular Medicine.

Dr. Jan Mašek began this project while a post doc in the laboratory of Dr. Emma Andersson at the Department of Cell and Molecular Biology, Karolinska Institutet. The project continued as a collaboration, once Dr. Mašek established his own laboratory at Charles University in the Czech Republic.

Crucial collaborations with immunologists from Prof. Niklas Björkström’s team at the Department of Medicine, Huddinge, Karolinska Institutet, Dr. Jan Dobes’ lab at Charles University, and hepatologists from Dr. Martin Gregor’s lab at the Institute of Molecular Genetics in Prague were invaluable in bringing this interdisciplinary research to fruition.