BACKGROUND & AIMS: Biliary atresia (BA) is a pediatric inflammatory disease of the biliary system which leads to cirrhosis and the need for liver transplantation. One theory regarding etiology is that bile duct injury is due to virus-induced autoreactive T cell-mediated inflammation. Regulatory T cell (Treg) abnormalities in BA could result in unchecked bystander inflammation and autoimmunity targeting bile ducts. The aim of this study was to determine if Tregs are dysfunctional in the rotavirus-induced mouse model of BA (murine BA). METHODS: Murine BA resulted from infection of BALB/c neonates with Rhesus rotavirus (RRV). RESULTS: Liver Tregs from BA mice were decreased in number, activation marker expression, and suppressive function. Adoptive transfer studies revealed that RRV-infected mice that received Tregs had significantly increased survival (84%) compared to controls (12.5%). In addition, ablation of Tregs in older mice, followed by RRV infection, resulted in increased bile duct injury. CONCLUSIONS: These studies demonstrate that dysregulation of Tregs is present in murine BA and that diminished Treg function may be implicated in the pathogenesis of human BA. Published by Elsevier B.V.
BACKGROUND & AIMS:Biliary atresia (BA) is a pediatric inflammatory disease of the biliary system which leads to cirrhosis and the need for liver transplantation. One theory regarding etiology is that bile duct injury is due to virus-induced autoreactive T cell-mediated inflammation. Regulatory T cell (Treg) abnormalities in BA could result in unchecked bystander inflammation and autoimmunity targeting bile ducts. The aim of this study was to determine if Tregs are dysfunctional in the rotavirus-induced mouse model of BA (murine BA). METHODS:Murine BA resulted from infection of BALB/c neonates with Rhesus rotavirus (RRV). RESULTS: Liver Tregs from BA mice were decreased in number, activation marker expression, and suppressive function. Adoptive transfer studies revealed that RRV-infectedmice that received Tregs had significantly increased survival (84%) compared to controls (12.5%). In addition, ablation of Tregs in older mice, followed by RRV infection, resulted in increased bile duct injury. CONCLUSIONS: These studies demonstrate that dysregulation of Tregs is present in murine BA and that diminished Treg function may be implicated in the pathogenesis of human BA. Published by Elsevier B.V.
Authors: Maureen H Richards; Meghann Teague Getts; Joseph R Podojil; Young-Hee Jin; Byung S Kim; Stephen D Miller Journal: J Autoimmun Date: 2011-01-26 Impact factor: 7.094
Authors: Barrett H Barnes; Rebecca M Tucker; Fabian Wehrmann; Doug G Mack; Yoshiyuki Ueno; Cara L Mack Journal: Liver Int Date: 2008-11-15 Impact factor: 5.828
Authors: Stephen M Brindley; Allison M Lanham; Frederick M Karrer; Rebecca M Tucker; Andrew P Fontenot; Cara L Mack Journal: Hepatology Date: 2012-04 Impact factor: 17.425
Authors: Brandy R Lu; Stephen M Brindley; Rebecca M Tucker; Cherie L Lambert; Cara L Mack Journal: Gastroenterology Date: 2010-07-23 Impact factor: 22.682
Authors: Paul L Bollyky; Ben A Falk; S Alice Long; Anton Preisinger; Kathy R Braun; Rebecca P Wu; Stephen P Evanko; Jane H Buckner; Thomas N Wight; Gerald T Nepom Journal: J Immunol Date: 2009-07-27 Impact factor: 5.422
Authors: Kristin Lorent; Weilong Gong; Kyung A Koo; Orith Waisbourd-Zinman; Sara Karjoo; Xiao Zhao; Ian Sealy; Ross N Kettleborough; Derek L Stemple; Peter A Windsor; Stephen J Whittaker; John R Porter; Rebecca G Wells; Michael Pack Journal: Sci Transl Med Date: 2015-05-06 Impact factor: 17.956
Authors: Cara L Mack; Cathie Spino; Estella M Alonso; Jorge A Bezerra; Jeffrey Moore; Catherine Goodhue; Vicky L Ng; Saul J Karpen; Veena Venkat; Kathleen M Loomes; Kasper Wang; Averell H Sherker; John C Magee; Ronald J Sokol Journal: J Pediatr Gastroenterol Nutr Date: 2019-04 Impact factor: 2.839