Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression.

ABSTRACT: The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation. We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis. To study this hypothesis, ARE-Del^+/- mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied. JAK inhibition resulted in a significant reduction in portal inflammation

SUBMITTER: Shao T 

PROVIDER: S-EPMC9508183 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature