Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia.
Biliary atresia (BA) is an inflammatory cholangiopathy of infancy. A proposed mechanism regarding the pathogenesis of BA is that of a virus-induced, immune-mediated injury to bile ducts. The rotavirus (RRV)-induced murine model of BA was utilized to determine the hepatic inflammatory response related to ductal obstruction and if the immune response recapitulated human BA. One week after infection, there was a significant increase in liver CD4(+) T cells producing IFN-gamma and in macrophages producing TNF-alpha. The intrahepatic pattern of inflammation evolved rapidly from an initial predominant CD4(+) Th1 cellular response to a subsequent influx of activated macrophages producing TNF-alpha and iNOS. This immune response persisted despite viral clearance and was representative of the hepatic immune profile present in human BA. Utilization of the murine model of BA yielded mechanistic data that can provide much needed insight into the role played by different arms of the immune system related to the pathogenesis of human BA.
Mack
Cara L
CL
Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital, 1056 East 19th Avenue B290, Denver, CO 80218, USA. cara.mack@uchsc.edu
Tucker
Rebecca M
RM
Sokol
Ronald J
RJ
Kotzin
Brian L
BL
D000818:Animals; D000831:Animals, Newborn; D001656:Biliary Atresia / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004790:Enzyme Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006932:Hyperbilirubinemia; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012400:Rotavirus Infections / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse