Biliary epithelial cells and primary biliary cirrhosis: The role of liver‐infiltrating mononuclear cells
Biliary epithelial cells and primary biliary cirrhosis: The role of liver‐infiltrating mononuclear cells
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DOI：
10.1002/hep.22102
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发表时间：
2008-03
期刊：
影响因子：
13.5
通讯作者：
S. Shimoda;K. Harada;H. Niiro;T. Yoshizumi;Y. Soejima;A. Taketomi;Y. Maehara;K. Tsuneyama;Minoru Nakamura;A. Komori;K. Migita;Y. Nakanuma;H. Ishibashi;C. Selmi;M. Gershwin
中科院分区：
文献类型：
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作者：
S. Shimoda;K. Harada;H. Niiro;T. Yoshizumi;Y. Soejima;A. Taketomi;Y. Maehara;K. Tsuneyama;Minoru Nakamura;A. Komori;K. Migita;Y. Nakanuma;H. Ishibashi;C. Selmi;M. Gershwin
原发性胆汁性肝硬化（PBC）的特点是高度选择性的自身免疫性损伤肝内小胆管，尽管广泛分布的线粒体自身抗原。在此基础上，已经表明靶向的胆管上皮细胞（BEC）通过分泌趋化因子吸引免疫细胞在自身免疫的持续中发挥积极作用。为了解决这个问题，我们使用多种Toll样受体（TLR）配体以及自体肝浸润单核细胞（LMNC）挑战PBC患者和对照组的BEC，随后通过定量特定趋化因子测量BEC表型和趋化因子产生以及LMNC趋化性。我们的数据反映了PBC患者和对照组的BEC表达相似水平的TLR亚型、CD 40和人类白细胞抗原DRα（HLA-DR α），并在我们的实验条件下产生等量的趋化因子。然而，有趣的是，与对照相比，BEC表达的趋化因子引起PBC LMNCs的迁移增强。此外，将自体LMNC添加到PBC BEC中导致产生更高水平的趋化因子，并增强CD 40和HLA-DR α的表达。结论：我们认为PBC中BECs的促炎活性是继发于LMNCs的干预，本身并不确定。这些数据支持了BEC实际上是自身免疫损伤的“无辜受害者”的假设，并且适应性免疫应答在PBC中至关重要。（肝脏学2008年）
Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll‐like receptor (TLR) ligands as well as autologous liver‐infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRα (HLA‐DRα) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC‐expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA‐DRα. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact “innocent victims” of autoimmune injury and that the adaptive immune response is critical in PBC. (HEPATOLOGY 2008.)