AbstractAutoimmune liver diseases (AILD) include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). In AIH, PBC and PSC the immune system attacks the liver leading to tissue destruction (hepatocytes - liver parenchyma cells and biliary epithelial cells), scarring and eventually liver failure and liver cancer. There is no curative therapy for these diseases and patients gradually develop end stage liver cirrhosis and undergo liver transplantation.
We still do not know why the immune system turns on the liver in AILD but evidence suggests this may be in part due to a dysfunction of white blood cells called regulatory T cells which have evolved to suppress unwanted autoimmune responses. These cells are deficient or defective in AILD and thus unable to suppress the harmful autoimmune response. In animal models, regulatory T cells can switch off autoimmune responses when infused into animals with disease. Early trials in graft versus host disease suggest such an approach may work in human autoimmune diseases as well.
Our group has utilised liver infiltrating lymphocytes from our transplant programme to dissect the homing behavior, deep phenotype and function of Treg and Th17 in human livers. We recently completed AUTUMN trial which demonstrated that GMP grade Treg can home to inflamed autoimmune livers. We are now developing methods for isolating and growing large numbers of functional regulatory T cells form patients with autoimmune liver disease which suppress immune responses in the laboratory to apply these cells in patients with AILD as new therapy.