The roles for biliary epithelial cells as antigen presenting cells or target cells in primary biliary cirrhosis

胆管上皮细胞作为抗原呈递细胞或靶细胞在原发性胆汁性肝硬化中的作用

• 批准号: 17590657
• 负责人: SHIMODA Shinji
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERCIT
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590657/
• 关键词: primary biliary cirrhosis; biliary epithelial cells; toll-like receptor; antigen presenting cells; target cells; chemokine; T細胞クローン; 胆管上皮細胞株

Biliary epithelial cells-(BEC) which established from disease liver in liver transplantation from.Primary biliary cirrhosis expressed CD40 and Toll-like receptor (TLR)2,3 and 4. BEC were examined whether they have roles as antigen presenting cells. Auto antigen pyruvate dehydrogenase complex E2 component (PDC-E2) 163-176 peptide was pulsed to BEC, and PDC-E2 163-176 reactive T cell clones (TCC) were co-coltured with the peptide profsed BEC, an TCC profiferation assay were performed. In some cases, BEC were pre-incubated with IFN-γ, CD40 ligand, TLR2,3,or 4 ligand. In all cases BEC could not proliferate TCC. BEC could not express co-stimulation molecules, CD80 or CD86 even after stimulated with IFN-γ, CD40 ligand, TLR2,3,or 4 ligand.Next BEC were examined whether sensitivity as target cells are increased after stimulated with IFN-y, CD40 ligand, TLR2,3,or 4 ligand. BEC have roles as target cells after stimulated with IFN-y, on the other hand BEC did not have roles as target cells with other stimulation.Finally chemokine CXCL8,CCL2,CXCL9,CXCL10,CX3CL1 and CXCL16 production from BEC were examined with or without the stimulation of IFN-γ, TLR2,3,or 4 ligand. BEC produced CXCL8 and CCL2 spontaneously. CXCL10,CX3CL1 and CXCL1G were produced after the stimulation with TLR3 ligand. IFN-γ increased the production of such chemokines.In conclusion, BEC were clarified that they do not have roles as antigen presenting cells, that IFN-g stimulation turn BEC as target cells but other stimulation did not affect BEC as target. cells, and that BEC produce chemokines spontaneously or uniquely with TLR3 ligand.

胆汁上皮细胞(BEC)是在肝移植过程中由病肝分化而来的细胞，表达CD40和Toll样受体(TLR)2、3和4。将自身抗原丙酮酸脱氢酶复合体E_2组分(PDC-E_2)163-176肽冲击BEC，并将PDC-E_2 163-176反应性T细胞克隆(TCC)与PDC-E_2反应性T细胞克隆(TCC)共染色，进行TCC扩增试验。在某些情况下，BEC预先与干扰素-γ、CD40L、TLR2、3或4L共同孵育。在所有病例中，BEC均不能增殖TCC。BEC经干扰素-γ、CD40L、TLR2、3、4配体刺激后仍不表达共刺激分子CD80或CD86。体外培养的BEC在干扰素-γ、TLR2、3、4配体的刺激下，产生趋化因子CXCL8、CCL2、CXCL9、CXCL10、CX3CL1和CXCL16。BEC自发产生CXCL8和CCL2。TLR3配体刺激后产生CXCL10、CX3CL1和CXCL1G。结论：BEC不具有抗原提呈细胞的作用，干扰素-γ刺激使BEC成为靶细胞，而其他刺激不影响BEC作为靶细胞。细胞，BEC自发地或与TLR3配体唯一地产生趋化因子。

项目成果

Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation

• DOI: 10.1097/01.tp.0000235186.30113.c7
• 发表时间: 2006-09-27
• 期刊: TRANSPLANTATION
• 影响因子: 6.2
• 作者: Kawano, Noriaki;Shimoda, Kazuya;Harada, Mine
• 通讯作者: Harada, Mine

Fractalkine and CX3CR1 are involved in the recruitment of Intraepithelial lymphocytes of intrahepatic bile ducts

• DOI: 10.1002/hep.20582
• 发表时间: 2005-03-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Isse, K;Harada, K;Nakanuma, Y
• 通讯作者: Nakanuma, Y

Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis

• DOI: 10.1016/j.jaut.2005.10.007
• 发表时间: 2006-03-01
• 期刊: JOURNAL OF AUTOIMMUNITY
• 影响因子: 12.8
• 作者: Nakamura, M;Takii, Y;Ishibashi, H
• 通讯作者: Ishibashi, H

Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases

• DOI: 10.1002/hep.20494
• 发表时间: 2005-01-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Kamihira, T;Shimoda, S;Harada, M
• 通讯作者: Harada, M

Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory

• DOI: 10.1053/j.gastro.2006.05.056
• 发表时间: 2006-08-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Shimoda, Shinji;Ishikawa, Fumihiko;Harada, Mine
• 通讯作者: Harada, Mine