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William M. Ridgway, MDAssociate Professor; Director of Division of Immunology, Allergy and RheumatologyDepartment of Medicine; Division of Immunology, Allergy and Rheumatology
Dr. Ridgway investigates the immunogenetic mechanisms of spontaneous autoimmune biliary disease (ABD) in NOD congenic mice, as well as a spontaneous PBC-like disease in dnTGF-βRII mice. The NOD congenic mice were bred to resist Type One Diabetes (i.e., no evidence of diabetes), but instead develop spontaneous autoimmune biliary disease. He has studied these mice in collaboration with Dr. Linda Wicker of Cambridge University and Dr. Eric Gershwin of UC Davis Medical Center. Dr Gershwin has identified anti-pyruvate dehydrogenase (PDH) antibodies in these mice, the hallmark of primary biliary cirrhosis in humans. This was the first animal model to spontaneously develop anti-PDH autoantibodies. Dr. Ridgway and colleagues have performed a series of experiments on intrahepatic lymphocyte populations from diseased and non-diseased mice to discover the cellular immunogenetic mechanisms of autoimmune biliary disease in these mice. Dr. Ridgeway’s goal in the NOD congenic work is to discover the immunogenetic basis of disease in this model, with the hope of further understand enigmatic human autoimmune biliary diseases such as primary biliary cirrhosis. The goal of the work on the dnTGF-βRII mice is to understand how the dominant negative transgene can impart biliary autoreactivity to CD8 cells.
Dr. Ridgway collaborates with Drs. Bezerra and Mattner identifying the immunogenetic mechanisms involved in the pathogenesis of biliary atresia and primary biliary cirrhosis. Projection of Core use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.
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(A) Liver histology was examined at 8 weeks after splenic CD8+ T-cell transfer in the presence or absence of CD19+ B cells from PC or spleen (Sp) of dnTGF-bRII mice into Rag-1–/– mice. Degrees of cellular infiltrates were less around bile ducts in mice receiving CD8+T cells + PC-B cells (Blue and black scale bars indicate 400 μm and 100 μm, respectively, in A; from Gastroenterology, 2009;3:1037-1047.
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