Primary biliary cholangitis (PBC), an autoimmune liver disease occurring predominantly in women, is characterized by high titers of serum anti-mitochondrial antibodies (AMAs) and progressive intrahepatic cholestasis. The immune system plays a critical role in PBC pathogenesis and a variety of immune cell subsets have been shown to infiltrate the portal tract areas of patients with PBC. Amongst the participating immune cells, CD4 T cells are important cytokine-producing cells that foster an inflammatory microenvironment. Specifically, these cells orchestrate activation of other immune cells, including autoreactive effector CD8 T cells that cause biliary epithelial cell (BEC) injury and B cells that produce large quantities of AMAs. Meanwhile, other immune cells, including dendritic cells (DCs), natural killer (NK) cells, NKT cells, monocytes, and macrophages are also important in PBC pathogenesis. Activation of these cells initiates and perpetuates bile duct damage in PBC patients, leading to intrahepatic cholestasis, hepatic damage, liver fibrosis, and eventually cirrhosis or even liver failure. Taken together, the body of accumulated clinical and experimental evidence has enhanced our understanding of the immunopathogenesis of PBC and suggests that immunotherapy may be a promising treatment option. Herein, we summarize current knowledge regarding immunological abnormalities of PBC patients, with emphasis on underlying pathogenic mechanisms. The differential immune response which occurs over decades of disease activity suggests that different therapies may be needed at different stages of disease.

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