A domestic research team is attracting attention by discovering the genetic cause of autoimmune liver disease that causes chronic fatigue.
Kangnam Severance Hospital Department of Laboratory Medicine Professor Lee Kyung-ah, Yonsei University College of Medicine Department of Biomedical Science Professors Kim Rak-gyun and Do So-hee, Laboratory Medicine Department Professor Shin Sae-am, and Hallym University Gangnam Sacred Heart Hospital Professor Park Sang-hoon’s team )’ was announced on the 16th.
Autoimmune liver disease is a disease in which the immune system abnormally judges one’s liver cells as pathogens and causes inflammation on its own. It accounts for about 5% of all liver diseases.
Primary biliary cholangitis (PBC) is a disease in which inflammation in the portal vein and bile duct damage in the liver progresses chronically, resulting in cholestasis, destruction of hepatocytes and fibrosis, and progressing to cirrhosis.
The pathogenesis of PBC has not been precisely elucidated, but environmental and genetic factors, such as infections and chemicals, are known to play a role.
The research team analyzed the genome of a rare family in which all four sisters were diagnosed with PBC to identify the genetic factors associated with the onset of PBC. did.
Separately, as a result of analyzing the nucleotide sequences of 62 patients with PBC, mutations in caspase-10 were observed at a frequency 10 times higher (P=0.002) in patients with PBC than in the general population.
Caspase is a proteolytic enzyme involved in cell death, inflammation, and autoimmunity, and acts as an important factor in tumor development and autoimmune diseases. However, little is known about the function of caspase-10 in the human body.
Accordingly, the research team utilized the CRISPR/Cas9 technology, a gene editing technology, to identify the role of caspase-10 in PBC development. After creating a cell line from which the 8 gene was removed and a cell line from which the caspase-10 gene was removed, the differences were investigated.
As a result, unlike caspase-8, caspase-10 does not play a significant role during the process of differentiation into macrophages, but after differentiation, it was found that it strongly regulates the inflammatory cell death process.
In addition, it was confirmed that liver fibrosis can be promoted in macrophages in which the caspase-10 gene has been deleted, and that this progression can be inhibited by administering ursodeoxycholic acid and obeticholic acid, which are currently approved as PBC treatment drugs.
Professor Rakkyun Kim said, “This is the first study to identify that a defect in caspase-10 function in macrophages affects the pathogenesis of PBC.” I hope to be able to,” he said.
The study was published in the international journal ‘Journal of Autoimmunity’ under the title ‘Caspase-10 affects the pathogenesis of primary biliary cholangitis by regulating inflammatory cell death’.