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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 6
Jun.  2011
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Cellular mechanism of immunopathogenesis of primary biliary cirrhosis

  • Published Date: 2011-06-20
  • Primary biliary cirrhosis (PBC) is a progressive, organ-specific autoimmune disease that predominantly affects woman and is characterized by lymphocytic infiltration in portal tracts, immune-mediated destruction of small intrahepatic small bile ducts, and the presence of high titers of serum anti-mitochondrial Abs (AMAs) .A murine model of PBC, generated by expressing a dominant-negative form of TGFβ receptor type Ⅱ (dnTGFβRⅡ) under the direction of the CD4 promoter, demonstrates several key features of human PBC and has been applied in previous PBC studies.Experimental data from Rag1-/-, μ-/-and CD1d-/-mice on a dnTGFβRⅡ background indicated that T cells, B cells and CD1d-restricted NKT cells plays critical roles in liver injury.Moreover, based on a rigorous series of cellular immunological studies, it is concluded that CD8+, but not CD4+ T cells, play a prominent role in mediating pathogenesis, and that B cells can have a suppressive regulatory effect on the infiammatory response besides just secreting auto-antibodies.These studies provide substantial evidence for a cellular mechanism in human primary biliary cirrhosis pathogenesis.

     

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