A MedUni Vienna study team has identified the role of a specific subtype of macrophages (white blood cells) in progressive non-alcoholic fatty liver disease. As part of the immune system, these cells have a protective function against liver fibrosis and cirrhosis. At the same time, they are useful as biomarkers of liver disease progression because they can be measured by a blood test. The results were recently published in the famous “Journal of Hepatology“.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and is estimated to affect approximately 30% of the European population. Chronic non-alcoholic fatty liver disease can progress to irreversible cirrhosis of the liver, which can only be cured by liver transplantation. Therefore, early identification of patients with non-alcoholic fatty liver disease is particularly important.
The pathogenesis (development) of non-alcoholic fatty liver disease, in particular advanced steatohepatitis (NASH, also: non-alcoholic fatty hepatic hepatitis), is associated with profound changes in the immune cells of the liver. Recently, increased accumulation of a subtype of macrophages that express high levels of the TREM2 receptor has been described in fatty liver disease.
However, the role of TREM2 positive macrophages in non-alcoholic fatty liver disease was so far unknown. The MedUni Vienna research team led by Christoph Binder and Tim Hendrikx from the Department of Laboratory Medicine was able to show in an animal model that these specific macrophages have a protective function in fibrosis – a precursor to cirrhosis of the liver. These cells are found in greatest numbers in affected areas of the liver during liver inflammation associated with non-alcoholic fatty liver disease, where they particularly accumulate in areas of cell damage and fibrosis.
The interdisciplinary study team also demonstrated in bone marrow transplant models that hematopoietic TREM2 deficiency prevents efficient fat storage and the breakdown of excess connective tissue (extracellular matrix), resulting in increased steatohepatitis, cell death and fibrosis. Therefore, TREM2-positive macrophages perform an important protective function in non-alcoholic fatty liver disease, where they prevent fat accumulation, inflammatory processes and disease progression to liver fibrosis. “It might be possible to develop new therapeutic approaches to treat fatty liver disease by enhancing this protective function of TREM2-positive macrophages,” said Florentina Porsch, co-first author of the study.
TREM2 exists both as a membrane receptor on cells and as a soluble form (sTREM2) detectable in blood. The role of this soluble form in the immune system is not yet clear. However, the study authors found that it is useful in patients to determine current disease status and helps distinguish between different stages of fatty liver disease much better than previously known biomarkers used in clinical practice. . “The soluble form of TREM2 is an excellent biomarker for identifying and staging advanced liver disease, which can progress from fatty liver disease to incurable cirrhosis if left untreated,” says first author Tim Hendrikx from the Department of Medicine. laboratory of MedUni Vienna.
Journal of Hepatology
The title of the article
Soluble TREM2 levels reflect recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH.
Publication date of articles
June 21, 2022
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