Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases
Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases
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DOI：
10.1002/hep.20494
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发表时间：
2005-01-01
期刊：
影响因子：
13.5
通讯作者：
Harada, M
中科院分区：
文献类型：
--
作者：
Kamihira, T;Shimoda, S;Harada, M
胆道上皮细胞（BEC）是几种人类免疫介导的肝脏疾病（包括原发性胆汁性肝硬化）的靶标，但目前尚不清楚BEC是作为辅助细胞还是抗原提呈细胞，尽管已有文献证实BEC表达高水平的人白细胞抗原II类、细胞间粘附分子-1和淋巴细胞功能相关抗原-3。为了研究这个问题，我们从原发性胆汁性肝硬化患者的白细胞抗原dr53中建立了自身反应性t细胞克隆，并将BEC功能表征为BECs调节t细胞活化的能力。我们在此报道，becc介导的t细胞激活部分通过程序性死亡1配体以细胞接触依赖的方式发生。此外，这种激活通过与细胞接触无关的方式产生前列腺素E2而发生。此外，前列腺素E2的产生部分受白细胞介素-1 β和肿瘤坏死因子α的控制。综上所述，BECs的调控活性对于维持外周免疫耐受具有重要意义。此外，BEC功能的调节可用于治疗调节。
The biliary epithelial cell (BEC) is the target for several human immune mediated liver diseases, including primary biliary cirrhosis, but it is not always clear whether the BEC functions as an accessory cell or an antigen presenting cell, although it is well documented that BECs express high levels of human leukocyte antigen Class II, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3. To examine this issue, we established autoreactive T-cell clones from human leukocyte antigen-DR53 patients with primary biliary cirrhosis and characterized BEC function as a function of the ability of BECs to regulate T-cell activation. We report herein that BEC-mediated T-cell activation occurs partially via programmed death 1 ligands in a cell-contact-dependent manner. Further, such activation occurs via prostaglandin E2 production in a cell-contact-independent fashion. Moreover, the production of prostaglandin E2 was partially controlled by interleukin-1beta and tumor necrosis factor alpha. In conclusion, the regulatory activities of BECs are important for the maintenance of peripheral immune tolerance. Further, modulation of BEC function may be used for therapeutic modulation.