Treg-specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma
Treg-specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma
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DOI：
10.1002/iub.1378
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发表时间：
2015-05-01
期刊：
影响因子：
4.6
通讯作者：
Li, Wei-Min
中科院分区：
文献类型：
--
作者：
Liu, Hao-Run;Li, Wei-Min
在某些独特的病症中，如肝脏的病毒感染，如乙型肝炎B（HBV）和丙型肝炎（HCV），T-STAT的激活可能与病毒感染的慢性化和随后通过整合的病毒基因组发展成肝细胞癌（HCC）的易感性相关。与此同时，潜在的持续性T细胞活化可能导致癌细胞的免疫逃避，从而导致癌性病症的持续。在这项研究中，我们假设，虽然相对比例的T-β 1可能保持不变，肝癌，持续的活动的T-β 1可能会导致免疫逃避在肝癌的晚期。为了研究T-reg在肝癌发病机制中的激活问题，我们获得了晚期HCC患者的肝活检和外周血样本，分离了T-reg，并检查了T-reg特异性去甲基化区域（TSDR）的甲基化状态，TSDR是一个关键区域，其甲基化抑制Treg活性，去甲基化刺激其基因组活性。这项研究提供了TSDR去甲基化，荧光素酶检测基因表达增加，以及在晚期HCC中CD 4 + CD 25 + FoxP 3调节性T细胞中作为基因增强子的关键转录因子核转位的证据。(c)2015 IUBMB Life，2015 67（5）：355-360，2015
In certain unique conditions like viral infections of the liver like hepatitis B (HBV) and hepatitis C (HCV), activation of T-regs may be associated with chronicity of the viral infections and subsequent predisposition to development of hepatocellular carcinoma (HCC) by the integrated viral genome. In parallel, potential persistence of T-regs activity may lead to immune evasion of cancerous cells and thus persistence of the carcinomatous conditions. In this study, we hypothesized that although the relative proportions of T-regs may remain unaltered in HCC, persistence of activity of T-regs may lead to immune evasion in advanced stages of HCC. To examine the issue of activation of T-reg in liver cancer pathogenesis, we obtained liver biopsy and peripheral blood samples from patients with advanced grades of HCC, isolated T-regs, and examined the methylation status of T-reg-specific demethylated region (TSDR), a key region whose methylation suppresses Treg activity and demethylation stimulates its genomic activity. This study provides evidence of demethylation of TSDR, increased gene expression examined by luciferase assays, and nuclear translocation of key transcription factors that function as gene enhancers in CD4+CD25+FoxP3 regulatory T cells in advanced grades of HCC. (c) 2015 IUBMB Life, 2015 67(5):355-360, 2015