慢加急性乙型肝炎肝衰竭患者肝组织树突状细胞特点研究*

doi:10.3969/j.issn.1672-5069.2012.05.0010

实用肝脏病杂志 ›› 2012, Vol. 15 ›› Issue (5): 400-403.doi: 10.3969/j.issn.1672-5069.2012.05.0010

慢加急性乙型肝炎肝衰竭患者肝组织树突状细胞特点研究^*

李保森, 孙颖, 张连业, 张政, 张伟, 赵军, 滕光菊, 常彬霞, 王福生, 邹正升

100039北京市解放军第302医院非感染性肝病诊疗中心（李保森,孙颖,张伟,赵军,滕光菊,常彬霞,邹正升）;
肝病生物治疗与研究中心（张政,王福生）;
安徽省太和县中医院（张连业）

收稿日期:2012-01-10 出版日期:2012-10-10 发布日期:2017-03-09
通讯作者: 邹正升, E-mail:zszou302@yahoo.com.cn
作者简介:李保森男,49岁,主任医师。主要从事肝脏病学临床诊治及发病机制研究
基金资助:
国家自然科学基金项目（基金编号30571749）

Intrahepatic dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure

Li Baosen, Sun Ying, Zhang Lianye, et al.

Center for Non-Infectious Liver Diseases,302nd Hospital of PLA,Beijing 100039,China

Received:2012-01-10 Online:2012-10-10 Published:2017-03-09

摘要/Abstract

摘要： 目的观察慢加急性乙型肝炎肝衰竭（Acute-on-chronic hepatitis B liver failure,ACHBLF）患者外周血和肝组织树突状细胞及其亚群的分布特征。方法选择11例进行肝移植的ACHBLF、10例慢性乙型肝炎患者和5例健康人,取外周血和肝组织,使用流式细胞仪计数外周血单个核细胞（PBMCs）和肝内浸润淋巴细胞（LILs）中浆样树突细胞（plasmacytoid DC,DCs）和髓样树突细胞（myeloid DC,mDCs）的频率,应用polyI:C 和CpG2216刺激培养PBMCs和LILs,采用ELISA法检测上清IFN-α、IL-12和IL-10水平;采用免疫组化技术检测肝内pDC和mDC的分布。结果 ACHBLF患者肝内pDCs与外周血pDCs频率具有显著性差异（P<0.05）,而肝内mDC的频率与外周血之间差异无统计学意义（P>0.05）;ACLF患者经刺激的PBMCs和LILs能够分泌IFN-α和IL-12,但LILs分泌细胞因子的水平较PBMCs明显降低,而分泌IL-10却较PBMCs明显升高;ACHBLF患者肝组织浸润了大量的pDCs和mDCs。结论 ACHBLF患者肝内浸润大量的DC亚群细胞,并优先分泌IL-10,在发病机制中可能具有局部的免疫调节作用。

关键词: 慢加急性肝衰竭, 浆样树突细胞, 髓样树突细胞

Abstract: Objective To characterize the dendrictic cell subsets in peripheral blood and liver tissues of patients with hepatitis B-related acute-on-chronic liver failure（ACHBLF）. Methods 11 patients with ACHBLF who had undergone liver transplantation,10 patients with chronic hepatitis B and 5 healthy persons were enrolled in this study,and their liver tissue samples and peripheral blood were collected. The proportion of myeloid DC（mDC）and plasmatoid DC（pDC）in peripheral blood mononuclear cells（PBMCs） and liver-infiltrating lymphocytes（LILs） were detected by flow cytometric analysis. The IFN- alpha,IL-12 and IL-10 levels in the supernatants by PBMCs and LILs were investigated by ELISA when they were stimulated with polyI:C or CpG2216,respectively. The prevalence of pDC and mDC in liver tissues were also assessed by immunohistochemical techniques. Results The number of intrahepatic pDCs was significantly higher than in peripheral blood in ACHBLF patients,but no difference was found between in mDC and PBMCs;The IFN-alpha and IL-12 levels were remarkably lower in LILs than in PBMCs,but IL-10 was higher when stimulated with DC-specific stimulator,polyI:C,CpG2216 and IL-3;The mDCs and pDCs were found to be infiltrated in the livers of ACHBLF patients as compared with CHB or healthy subjects. Conclusions The intrahepatic DC subsets preferentially produces IL-10,which might exert an important role in immune regulation in situ of livers of ALHBLF patients.

Key words: Acute-on-chronic liver failure, Myeloid dendritic cells, Plasmacytoid dendritic cells

李保森, 孙颖, 张连业, 张政, 张伟, 赵军, 滕光菊, 常彬霞, 王福生, 邹正升. 慢加急性乙型肝炎肝衰竭患者肝组织树突状细胞特点研究^*[J]. 实用肝脏病杂志, 2012, 15(5): 400-403.

Li Baosen, Sun Ying, Zhang Lianye, et al.. Intrahepatic dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2012, 15(5): 400-403.

参考文献

[1] Rehermann B,Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol,2005,5（3）:215-229.
[2] Sen S,Williams R,Jalan R. The pathophysiological basis of acute-on-chronic liver failure. Liver,2002,22 Suppl 2:5-13.
[3] Seto WK,Lai CL,Yuen MF. Acute-on-chronic liver failure in chronic?hepatitis B. J Gastroenterol Hepatol,2011,doi:10.1111/j.1440-1746.2011.06971.x.
[4] Garg H,Kumar A,Garg V,et al. Clinical profile and predictors of mortality in patients of acute-on-chronicliver failure. Dig Liver Dis,2012,44（2）:166-171.
[5] Huang K,Hu JH,Wang HF,et al. Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol,2011,17（29）:3448-3452.
[6] Wasmuth HE,Kunz D,Yagmur E,et al. Patients with acute on chronic liver failure display“sepsis-like”immune paralysis. J Hepatol,2005,42（2）:195-201.
[7] Liu YJ. IPC: Professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol, 2005,23:275-306.
[8] Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol,2003,3（1）:51-62.
[9] Lau AH,Thomson AW. Dendritic cells and immune regulation in the liver. Gut,2003,52（2）:307-314.
[10] Goddard S,Youster J,Morgan E,et al. Interleukin-10 secretion differentiates dendritic cells from human liver and skin. Am J Pathol,2004,164（2）:511-519.
[11] Tanimoto K,Akbar SM,Michitaka K,et al. Antigen-presenting cells at the liver tissue in patients with chronic viral liver diseases: CD83-positive mature dendritic cells at the vicinity of focal and confluent necrosis. Hepatol Res,2001,21（2）:117-125.
[12] Kunitani H,Shimizu Y,Murata H,et al. Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases. J Hepatol,2002,36（6）:734-741.
[13] Zhang Z,Chen D,Yao J,et al. Increased infiltration of intrahepatic DC subsets closely correlate with viral control and liver injury in immune active pediatric patients with chronic hepatitis B. Clin Immunol,2007,122（2）:173-180.
[14] Lai WK,Curbishley SM,Goddard S,et al. Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell function. J Hepatol,2007,47（3）:338-347.
[15] 中华医学会感染病学分会肝衰竭与人工肝学组,中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊疗指南.实用肝脏病杂志,2006,9（6）:321-324.
[16] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志,2011,14（2）:81-89.
[17] Xu D,Fu J, Jin L,et al. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol,2006,177（1）:739-747.
[18] Guidotti LG,Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol,2006,1:23-61.
[19] Rastogi A,Kumar A,Sakhuja P,et al. Liver histology as predictor of outcome in patients with acute-on-chronic liver failure （ACLF）. Virchows Arch,2011,459（2）:121-127.
[20] Van Der Molen RG,Sprengers D,Biesta PJ,et al. Favorable effect of adefovir on the number and functionality of myeloid dendritic cells of patients with chronic HBV. Hepatology,2006,44（4）:907-914.
[21] Kimura K,Kakimi K,Wieland S,et al. Activated intrahepatic antigen-presenting cells inhibit hepatitis B virus replication in the liver of transgenic mice. J Immunol,2002,169（9）:5188-5195.
[22] Dunn C,Brunetto M,Reynolds G,et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med,2007,204（3）:667-680.
[23] Leifeld L,Cheng S,Ramakers J,et al. Imbalanced intrahepatic expression of interleukin 12,interferon gamma,and interleukin 10 in fulminant hepatitis B. Hepatology,2002,36（4 Pt 1）:1001-1008.
[24] 戚朝霞,于淑霞,郝洪升,等.慢加急性肝衰竭中IL-10的表达及其启动子甲基化状态的研究.中华实验和临床病毒学杂志,2011,25（2）:99-101.

慢加急性乙型肝炎肝衰竭患者肝组织树突状细胞特点研究^*

Intrahepatic dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure

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