B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.

A leading theory regarding the pathogenesis of biliary atresia (BA) is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this s...

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Autores principales:	Amy G Feldman, Rebecca M Tucker, Erika K Fenner, Roberta Pelanda, Cara L Mack
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/590002222cf24d0891dae1ce4907c617
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spelling	oai:doaj.org-article:590002222cf24d0891dae1ce4907c6172021-11-18T08:58:30ZB cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.1932-620310.1371/journal.pone.0073644https://doaj.org/article/590002222cf24d0891dae1ce4907c6172013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23991203/?tool=EBIhttps://doaj.org/toc/1932-6203A leading theory regarding the pathogenesis of biliary atresia (BA) is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this study was to determine the role of B cells in the development of biliary obstruction in the Rhesus rotavirus (RRV)-induced mouse model of BA. Wild-type (WT) and B cell-deficient (Ig-α(-/-)) mice received RRV shortly after birth. Ig-α(-/-) RRV-infected mice had significantly increased disease-free survival rate compared to WT RRV-infected BA mice (76.8% vs. 17.5%). In stark contrast to the RRV-infected BA mice, the RRV-infected Ig-α(-/-) mice did not have hyperbilirubinemia or bile duct obstruction. The RRV-infected Ig-α(-/-) mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-α(-/-) mice had significantly increased numbers of regulatory T cells (Tregs) at baseline and after RRV infection compared to WT mice. However, depletion of Tregs in Ig-α(-/-) mice did not induce biliary obstruction, indicating that the expanded Tregs in the Ig-α(-/-) mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-α(-/-) mice are protected from biliary obstruction in the RRV-induced mouse model of BA, indicating a primary role of B cells in mediating disease pathology. The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA.Amy G FeldmanRebecca M TuckerErika K FennerRoberta PelandaCara L MackPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e73644 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy G Feldman Rebecca M Tucker Erika K Fenner Roberta Pelanda Cara L Mack B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
description	A leading theory regarding the pathogenesis of biliary atresia (BA) is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this study was to determine the role of B cells in the development of biliary obstruction in the Rhesus rotavirus (RRV)-induced mouse model of BA. Wild-type (WT) and B cell-deficient (Ig-α(-/-)) mice received RRV shortly after birth. Ig-α(-/-) RRV-infected mice had significantly increased disease-free survival rate compared to WT RRV-infected BA mice (76.8% vs. 17.5%). In stark contrast to the RRV-infected BA mice, the RRV-infected Ig-α(-/-) mice did not have hyperbilirubinemia or bile duct obstruction. The RRV-infected Ig-α(-/-) mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-α(-/-) mice had significantly increased numbers of regulatory T cells (Tregs) at baseline and after RRV infection compared to WT mice. However, depletion of Tregs in Ig-α(-/-) mice did not induce biliary obstruction, indicating that the expanded Tregs in the Ig-α(-/-) mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-α(-/-) mice are protected from biliary obstruction in the RRV-induced mouse model of BA, indicating a primary role of B cells in mediating disease pathology. The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA.
format	article
author	Amy G Feldman Rebecca M Tucker Erika K Fenner Roberta Pelanda Cara L Mack
author_facet	Amy G Feldman Rebecca M Tucker Erika K Fenner Roberta Pelanda Cara L Mack
author_sort	Amy G Feldman
title	B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
title_short	B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
title_full	B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
title_fullStr	B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
title_full_unstemmed	B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
title_sort	b cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/590002222cf24d0891dae1ce4907c617
work_keys_str_mv	AT amygfeldman bcelldeficientmiceareprotectedfrombiliaryobstructionintherotavirusinducedmousemodelofbiliaryatresia AT rebeccamtucker bcelldeficientmiceareprotectedfrombiliaryobstructionintherotavirusinducedmousemodelofbiliaryatresia AT erikakfenner bcelldeficientmiceareprotectedfrombiliaryobstructionintherotavirusinducedmousemodelofbiliaryatresia AT robertapelanda bcelldeficientmiceareprotectedfrombiliaryobstructionintherotavirusinducedmousemodelofbiliaryatresia AT caralmack bcelldeficientmiceareprotectedfrombiliaryobstructionintherotavirusinducedmousemodelofbiliaryatresia
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B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.

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