The role of miR-122 in autoimmune liver diseases

• Applicant: Professor Dr. Johannes Herkel
• Subject Area: Gastroenterology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544225272

The prevalence and incidence of autoimmune liver diseases (ALD) world-wide is increasing. The clinical and financial burden from this malady is also increasing. Current treatment options are insufficient in terms of efficacy, specificity and tolerability. Hence, despite medication, patients are at risk of progressing to liver cirrhosis and liver cancer. The literature and our preliminary results show that the liver’s unique immune privileged microenvironment is disrupted in ALD. Furthermore, we show that the hepatic micro-RNA miR-122 is a regulator of the liver immune privileged state, which is significantly reduced in these chronic liver maladies. In addition, we show that miR-122 is also a regulator of hepatic progenitor cell-driven carcinogenesis. Others and we also showed that miR-122 has tumor suppressor properties. Therefore, we hypothesize that increasing liver tissue levels of miR-122 will serve the treatment of ALD both by re-inducing the immune tolerance state of the liver and preventing liver cancer development. We will increase miR-122 with a number of modalities, including a small molecule we developed for this and assess the preferred approach. These experimental therapies will be tested in suitable mouse models that allow examination of autoantigen-specific immune responses in the liver and inflammation-driven liver fibrosis and cancer. Moreover, we will perform functional studies with cells from ALD patients to confirm the therapeutic effect of mir-122 induction in humans and assess its translational potential.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professor Dr. Eithan Galun