Degeneration of intrahepatic bile duct with lymphocyte infiltration into biliary epithelial cells in biliary atresia

Ohya, Toshiki; Fujimoto, Toshio; Shimomura, Hiroshi; Miyano, Takeshi

doi:10.1016/0022-3468(95)90120-5

Cited by 75 publications

(53 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, lymphocyte permeation into bile duct epithelium has been previously described in human biliary atresia. 25 Within the SCID recipients of RRV-diseased T cells, the degree of periductal inflammation observed by hematoxylin-eosin stain was subjectively greater than what could be accounted for by the T cells detected by immunohistochemistry. Therefore, we hypothesized that recipient macrophages may be activated and attracted by T cell cytokines or chemokines and infiltrate into the site of injury.…”

Section: Adoptively Transferred T Cells From Rrv-diseased Mice Lead Tmentioning

confidence: 89%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

View full text Add to dashboard Cite

Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)-induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-␥-producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct-specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia-specific T cell-mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research.

show abstract

Section: Adoptively Transferred T Cells From Rrv-diseased Mice Lead Tmentioning

confidence: 89%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

View full text Add to dashboard Cite

show abstract

“…3,[36][37][38][39][40][41][42][43][44][45] In most cases, the biliary remnant from patients with BA has marked inflammation of the bile duct, extended segments in which there is damage to and necrosis of bile duct epithelium, and at least 1 segment in which the bile duct is obliterated. We did not see inflammation, necrosis, or obliteration of the extrahepatic biliary system in the inv mouse.…”

Section: Discussionmentioning

confidence: 99%

“…3,[36][37][38][39][40][41][42][43][44][45] In fact, Landing hypothesized a number of years ago that BA, choledochal cyst, and idiopathic neonatal hepatitis represented different manifestations of a single disease process termed ''infantile obstructive cholangiopathy.'' 46 In this hypothesis, injury could occur to a varying degree in the liver alone, bile duct alone, or both; injury to the bile duct epithelium could result in duct obliteration or weakening of the duct wall with subsequent dilatation and cyst formation or both.…”

Section: Discussionmentioning

confidence: 99%

Anomalous development of the hepatobiliary system in the inv mouse

et al. 1999

View full text Add to dashboard Cite

Extrahepatic biliary atresia (BA) is a devastating disease of the neonate in which the hepatic and/or common bile duct is obliterated or interrupted. Infants and children with this diagnosis constitute 50% to 60% of the pediatric population that undergoes orthotopic liver transplantation. However, there is still very little known about the etiology and pathogenesis of BA. Several recent studies have demonstrated that anomalies of situs determination are more commonly associated with BA than previously recognized. In this study, we examined the pathogenesis of jaundice in the inv mouse, a transgenic mouse in which a recessive deletion of the inversin gene results in situs inversus and jaundice. The results show that these mice have cholestasis with conjugated hyperbilirubinemia, failure to excrete technetium-labeled mebrofenin from the liver into the small intestine, lack of continuity between the extrahepatic biliary tree and the small intestine as demonstrated by Trypan blue cholangiography, and a liver histological picture indicative of extrahepatic biliary obstruction with negligible inflammation/necrosis within the hepatic parenchyma. Lectin histochemical staining of biliary epithelial cells in serial sections suggests the presence of several different anomalies in the architecture of the extrahepatic biliary system. These results suggest that the inversin gene plays an essential role in the morphogenesis of the hepatobiliary system and raise the possibility that alterations in the human orthologue of inversin account for some of the cases of BA in which there are also anomalies of situs determination. (HEPATOLOGY 1999;30:372-378.)

show abstract

“…In the inflammatory environment, naïve CD4 ϩ T cells differentiate to either Th1 effector cells (driven by IL-12 and producing IFN-␥, IL-2, TNF-␤, and TNF-␣) or Th2 effector cells (driven by IL-4 and producing IL-4, IL-5, and IL-10). In biliary atresia, T-cell infiltrates surround and invade intrahepatic bile ducts (37), characterized predominantly by CD4 ϩ T cells (38 -40), CD8 ϩ T cells (41), or a mixture of both (42) (see Fig. 2).…”

Section: T-cell-mediated Inflammation T-cell Activation Requires Thementioning

confidence: 99%

Unraveling the Pathogenesis and Etiology of Biliary Atresia

2005

View full text Add to dashboard Cite

Degeneration of intrahepatic bile duct with lymphocyte infiltration into biliary epithelial cells in biliary atresia

Cited by 75 publications

References 14 publications

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

Anomalous development of the hepatobiliary system in the inv mouse

Unraveling the Pathogenesis and Etiology of Biliary Atresia

Contact Info

Product

Resources

About