Wajahat Mehal,
Associate Professor,
Yale University
Dr. Mehal is an immunologist and liver physician at Yale university and his group works on liver inflammation and fibrosis using multiple animal models with a goal towards developing identifying novel pathways and new therapeutics.
Hepatocyte Circulating Mitochondrial DNA Drives Non-alcoholic Steatohepatitis by Activation of TLR9
Tuesday, 22 March 2016 at 14:30
Add to Calendar ▼2016-03-22 14:30:002016-03-22 15:30:00Europe/LondonHepatocyte Circulating Mitochondrial DNA Drives Non-alcoholic Steatohepatitis by Activation of TLR9SELECTBIOenquiries@selectbiosciences.com
Nonalcoholic steatohepatitis (NASH) is the most common liver disease in industrialized countries. NASH is a progressive disease that can lead to cirrhosis, cancer, and death, and there are currently no approved therapies. The development of NASH in animal models requires intact TLR9, but how the TLR9 pathway is activated in NASH is not clear. Our objectives in this study were to identify NASH-associated ligands for TLR9, establish the cellular requirement for TLR9, and evaluate the role of obesity-induced changes in TLR9 pathway activation. We demonstrated that plasma from mice and patients with NASH contains high levels of mitochondrial DNA (mtDNA) and intact mitochondria and has the ability to activate TLR9. Most of the plasma mtDNA was contained in microparticles (MPs) of hepatocyte origin, and removal of these MPs from plasma resulted in a substantial decrease in TLR9 activation capacity. In mice, NASH development in response to a high-fat diet required TLR9 on lysozyme-expressing cells, and a clinically applicable TLR9 antagonist blocked the development of NASH when given prophylactically and therapeutically. These data demonstrate that activation of the TLR9 pathway provides a link between the key metabolic and inflammatory phenotypes in NASH.
Add to Calendar ▼2016-03-22 14:30:002016-03-22 15:30:00Europe/LondonHepatocyte Circulating Mitochondrial DNA Drives Non-alcoholic Steatohepatitis by Activation of TLR9SELECTBIOenquiries@selectbiosciences.com
