Researchers from the Liver Disease group from the Osakidetza Biodonostia Medical Research Institute alongside researchers from Newcastle University and Vienna University, coordinated by Dr. Maria Jesus Perugorria, have just published in the prestigious journal Gut the results of an international collaborative study, describing the role that the TREM-2 anti-inflammatory receptor plays in protecting the liver in experimental models of chronic and acute liver damage, for the first time.

This article has been recently highlighted by the magazine Nature Reviews Gastroenterology & Hepatology too.

There has been an increased interest over the last few years in gut microbiota and its link with the progression of several diseases, in the study of the causes of a range of diseases. Bacterial translocation from the intestine to the liver (i.e., the passage of bacteria through the intestinal mucosa/barrier, due to a range of pathological processes) has also been described as a factor involved in the development and evolution of chronic liver diseases. It is therefore essential to gain detailed knowledge of the molecular mechanisms involved in the innate immune response of the liver to these bacterial components in order to discover new therapeutic targets.

This study is based on the premise that the levels of expression of the TREM2 receptor increase in both the liver samples of patients with cirrhosis as well as in mice with acute and chronic liver damage. This receptor has been shown to be capable of curbing inflammatory responses mediated by bacterial components, as well as protecting against acute liver damage, through the use of genetically modified mice. “These results could be of great value in the future, due to how strategies to activate this receptor could be beneficial for patients with these types of diseases”, explains the first author and coordinator of the study, Dr. María Jesús Perugorria (Researcher Ikerbasque, Ramón y Cajal and CIBERehd) from the Biodonostia Liver Disease group.

Based on these positive data obtained from this study and within the Carlos III Health Strategic Action, the role of TREM2 in hepatobiliary cancers, as well as in liver cancer and cholangiocarcinoma, will be studied over the next few years. The progression of chronic liver disease is characterised by the presence of chronic inflammation with progressive fibrosis that can lead to the development of cirrhosis, liver failure, and ultimately the development of hepatobiliary cancers. Although involving different diseases, tumours largely develop within the context of chronic liver disease, where the innate immune response and inflammation play an important role.

The research work has been supported by the Minister of Economy, Industry and Competitiveness (Ramón y Cajal programme), Instituto de Salud Carlos III (Subsidies for Research Projects in Health and CIBERehd), IKERBASQUE, Basque Country (SAIOTEK Programme) and the University of the Basque Country (UPV/EHU).

Reference:

Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage.
Perugorria MJ, Esparza-Baquer A, Oakley F, Labiano I, Korosec A, Jais A, Mann J, Tiniakos D, Santos-Laso A, Arbelaiz A, Gawish R, Sampedro A, Fontanellas A, Hijona E, Jimenez-Agüero R, Esterbauer H, Stoiber D, Bujanda L, Banales JM, Knapp S, Sharif O, Mann DA. Gut. 2018 Jan 27.