Defining and Targeting Autoimmune Liver Disease
The liver is the largest solid organ in the body and is critical for metabolic and immune functions, however huge gaps still exist in our basic knowledge of the human liver. Due to challenges in obtaining human liver tissue and the fragility of liver specimens, little is known about the cells that make up the human liver and its immune microenvironment: much of our current understanding is derived from studies in animal models. We recently generated a map of the cellular landscape of the healthy human liver using single cell RNA sequencing (scRN-seq), immunohistochemistry and flow cytometry: we will now extend these results to diseased human livers in order to define new treatments for immune-mediated liver disease. Autoimmune liver diseases, such as primary sclerosing cholangitis (PSC,) affect 0.5-1 in 100,000 adults and 1-16 in 100,000 children per year and has a higher prevalence in men than women. PSC is a progressive disease that destroys the biliary epithelium of the liver and many patients will eventually require a liver transplant as there is currently no effective therapy. PSC is thought to be aggravated by cells of the innate immune system, making targeted immune modulation an avenue for disease treatment.