by Medical University of Vienna

Credit: AI-generated image

Primary sclerosing cholangitis (PSC) is a rare, chronic inflammatory disease of the bile ducts and difficult to treat. Studies conducted by the Division of Gastroenterology and Hepatology at MedUni Wien under the guidance of Michael Trauner (Department of Internal Medicine III) were able to show positive effects from the administration of synthetically produced bile acids and bile acid receptor agonists. A recent joint study of Trauner and the Immunologist Nicole Boucheron shows for the first time that the synthetically manufactured bile acid Nor-UDCA (Nor-ursodeoxycholicacid) also acts directly on the immune system and CD8-T cells, which are misdirected in PSC. This can reduce tissue-damaging inflammation. The results of the study were published in the Journal of Hepatology.

"At the same time, we were able to decipher the mechanism behind this and show how exactly this happens," says the expert from the MedUni Wien Centre for Pathophysiology, Infectiology and Immunology, and explains further: "PSC causes the CD8 T cells to be misdirected, and nor-UDCA virtually guides them back onto the right path by regulating the protein mTOR and depriving the cells of the fuel they would require to cause further damage." CD8 T cells, when functioning normally, are actually there to fight viruses as well as cancer cells.

"This immunometabolic aspect is entirely new; we were able to show for the first time that bile acids have a direct impact on the immune system as therapeutically useful signaling molecules," adds Trauner. The therapy with the synthetic bile acid also has the effect of switching off the overreaction of the CD8 T-cells in the immune system and allowing them to resume their usual function in the specific elimination of virus-infected cells or cancer cells.

The findings of the study could lead to the therapeutic use of synthetically produced bile acid Nor-UDCA in the future for the treatment of other inflammatory diseases in which a misdirected immune system plays a role.

The study was conducted in collaboration between Michael Trauner's research group at the Department of Internal Medicine III with the Centre for Pathophysiology, Infectiology and Immunology and the CeMM (Research Centre for Molecular Medicine) and is funded by the Austrian Science Fund FWF.

PSC is a rare disease with a poor prognosis and can lead to cirrhosis of the liver and bile duct cancer. It affects 0.01 % of the population, but despite its rarity, PSC is responsible for more than 10 % of all liver transplants, making it the third most common indication for this surgical procedure in Europe.

More information: Ci Zhu et al, 24-Norursodeoxycholic acid reshapes immunometabolism in CD8+ T cells and alleviates hepatic inflammation, Journal of Hepatology (2021). DOI: 10.1016/j.jhep.2021.06.036

Provided by Medical University of Vienna