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KMID : 0381120210430111289
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Genes and Genomics
2021 Volume.43 No. 11 p.1289 ~ p.1299
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RRV-induced biliary atresia in neonatal mice involves CD8?+?T lymphocyte killer cells and the Notch signaling pathway
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Si Xinmin
Chen Ji
Huang Lei
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Abstract
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Background: Persistent inflammation induced by viral infection may contribute to the pathogenesis of biliary atresia (BA). Moreover, CD4+ helper cells and CD8+ killer cells are the main effector cells involved in BA and intrahepatic bile duct injuries.
Objective: Thus, we aimed to explore the dynamics of inflammatory cell infiltration and inflammation-regulated pathways in liver-specific inflammatory responses.
Methods: Neonatal Balb/C mice were intraperitoneally infected with 1?×?106 PFU rhesus rotavirus (RRV; BA?+?group), 1?×?105 PFU RRV (BA- group), or DMEM (control group). Mice were sacrificed 7 or 14 days post-infection and their bile ducts, livers, and spleen-derived tissues were examined via H & E staining. The number of CD4+T lymphocytes helper cells (CD4+Th), CD8+T lymphocytes killer cells (CD8+Tc), natural killer (NK) cells, and macrophages (Mac) in the liver and spleen were quantified by flow cytometry. The expression of inflammatory genes was analyzed via a PCR-array. Western blotting was conducted to quantify the protein expression of Notch receptor active fragments (NICD). Finally, some mice were injected with DAPT (a γ-secretase inhibitor) 12 h post-infection followed by analysis of liver and bile duct tissues after 14 days.
Results: The numbers of CD4+Th cells were increased in the livers of BA- mice after 14 days (P?
Conclusion: The DAPT-based intervention could reduce expression of CD8+Tc and bile duct damage in BA mouse livers post-RRV infection. We believe that the Notch signaling pathway regulates CD8+Tc functions and inflammatory dynamics in BA mouse livers.
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KEYWORD
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Biliary atresia, CD8 Tc, Neonatal mice, Animal model, Notch signaling pathway
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