Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and damage. This drives liver inflammation, promoting the progression to non-alcoholic steatohepatitis (NASH) and liver fibrosis. There are currently no approved therapies for NASH and fibrosis, which is in part due to a lack of knowledge of the immunological events underpinning NASH and fibrosis. The pathogenesis of NASH is strongly influenced by crosstalk with other tissues. There is increasing evidence that specifically obese adipose tissue macrophages (ATMs) are directly linked to liver pathology. In this respect, the host lab has shown that obese ATMs increase hepatic macrophage number. However, the exact changes in macrophage subsets and phenotypes were not investigated. I recently demonstrated that in NASH liver macrophages display large heterogeneity in phenotype and tissue localization and this plays a key role in NASH-associated liver fibrosis. Based on this combined preliminary data generated by the host lab and me, I hypothesize that ATMs alter hepatic macrophage composition and consequently affect the progression of NASH to liver fibrosis. By combining the mouse models and expertise available in the host lab and advanced technology present at the host institute, with my expertise in detailed immunophenotyping of the liver in NASH and fibrosis, I will address this innovative hypothesis in great detail. To bridge the translational gap from animal studies, I will investigate the potential contribution of ATMs to hepatic inflammation and fibrosis in humans by using unique fresh paired adipose tissue and liver biopsies available through the clinical network of the host lab. MacTalk integrates the scientific and technical expertise of both me and the host lab, creating a unique framework to identify novel mediators of hepatic inflammation and fibrosis. Furthermore, MacTalk will lay a strong foundation for my future career as independent researcher in the field of liver fibrosis.
Fields of science
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme