Primary sclerosing cholangitis: Therapy with synthetic bile acid acts directly on the immune system

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Primary Sclerosing Cholangitis (PSC) is a rare, chronic inflammatory disease of the bile ducts and is 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-ursodeoxycholic acid) 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 top journal '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 signalling molecules."

Michael Trauner, Department of Internal Medicine III, Medical University of Vienna

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.

Source:
Journal reference:

Zhu, C., et al. (2021) 24-Norursodeoxycholic acid reshapes immunometabolism in CD8+ T cells and alleviates hepatic inflammation. Journal of Hepatology. doi.org/10.1016/j.jhep.2021.06.036.

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