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Cytokine-Producing B Cells Promote Immune-Mediated Bile Duct Injury in Murine Biliary Atresia.
Bednarek, Joseph; Traxinger, Brianna; Brigham, Dania; Roach, Jonathan; Orlicky, David; Wang, Dong; Pelanda, Roberta; Mack, Cara L.
Afiliação
  • Bednarek J; Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Aurora, CO.
  • Traxinger B; Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Aurora, CO.
  • Brigham D; Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Aurora, CO.
  • Roach J; Department of Surgery, University of Colorado School of Medicine, Aurora, CO.
  • Orlicky D; Department of Pathology, University of Colorado School of Medicine, Aurora, CO.
  • Wang D; Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Aurora, CO.
  • Pelanda R; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • Mack CL; Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Aurora, CO.
Hepatology ; 68(5): 1890-1904, 2018 11.
Article em En | MEDLINE | ID: mdl-29679373
Biliary atresia (BA) is a neonatal T cell-mediated, inflammatory, sclerosing cholangiopathy. In the rhesus rotavirus (RRV)-induced neonatal mouse model of BA (murine BA), mice lacking B cells do not develop BA, and the lack of B cells is associated with loss of T-cell and macrophage activation. The aim of this study was to determine the mechanism of B cell-mediated immune activation (antigen presentation versus cytokine production) in murine BA. Normal neonatal B cells in the liver are predominantly at pro-B and pre-B cellular development. However, BA mice exhibit a significant increase in the number and activation status of mature liver B cells. Adoptively transferred B cells into RRV-infected, B cell-deficient mice were able to reinstate T-cell and macrophage infiltration and biliary injury. Nonetheless, neonatal liver B cells were incompetent at antigen presentation to T cells. Moreover, 3-83 immunoglobulin transgenic mice, in which B cells only present an irrelevant antigen, developed BA, indicating a B-cell antigen-independent mechanism. B cells from BA mice produced a variety of innate and adaptive immune cytokines associated with immune activation. In vitro trans-well studies revealed that BA B cells secreted cytokines that activated T cells based on increased expression of T-cell activation marker cluster of differentiation 69. Conclusion: Neonatal liver B cells are highly activated in murine BA and contribute to immune activation through production of numerous cytokines involved in innate and adaptive immunity; this work provides increased knowledge on the capacity of neonatal B cells to contribute to an inflammatory disease through cytokine-mediated mechanisms, and future studies should focus on targeting B cells as a therapeutic intervention in human BA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ductos Biliares / Atresia Biliar / Linfócitos B / Citocinas Limite: Adolescent / Animals / Child / Child, preschool / Humans Idioma: En Revista: Hepatology Ano de publicação: 2018 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ductos Biliares / Atresia Biliar / Linfócitos B / Citocinas Limite: Adolescent / Animals / Child / Child, preschool / Humans Idioma: En Revista: Hepatology Ano de publicação: 2018 Tipo de documento: Article País de publicação: Estados Unidos