原发性干燥综合征患者 CD4+T 细胞中 CD70（TNFSF7）的低甲基化和过表达。
Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sjögren's syndrome.
机构信息
Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
出版信息
J Dermatol Sci. 2010 Sep;59(3):198-203. doi: 10.1016/j.jdermsci.2010.06.011. Epub 2010 Jul 7.
BACKGROUND
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration and the production of autoantibodies, leading to the destruction of lacrimal and salivary glands. However, very little is known about the pathogenesis of the disorder. CD70 (TNFSF7), a B cell costimulatory molecule, is overexpressed in CD4(+) T cells from patients with systemic erythematosus lupus (SLE) due to the hypomethylation of its promoter.
OBJECTIVE
In this study we asked whether the epigenetic regulation of CD70 expression is abnormal in pSS.
METHODS
CD70 levels in CD4(+) T cells from pSS patients, tinea pedis and healthy controls were measured by real-time RT-PCR and flow cytometry. Bisulphite sequencing was performed to determine the methylation status of the TNFSF7 promoter region.
RESULTS
CD70 expression was significantly elevated and correlated with a decrease in TNFSF7 promoter methylation in pSS CD4(+) T cells compared to controls.
CONCLUSIONS
Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4(+) T cells, and may contribute to autoreactivity.
背景
原发性干燥综合征（pSS）是一种自身免疫性疾病，其特征为淋巴细胞浸润和自身抗体的产生，导致泪腺和唾液腺的破坏。然而，对于该疾病的发病机制知之甚少。CD70（TNFSF7）是一种 B 细胞共刺激分子，由于其启动子的低甲基化，系统性红斑狼疮（SLE）患者的 CD4+T 细胞中过度表达。
目的
在这项研究中，我们询问了 pSS 中 CD70 表达的表观遗传调控是否异常。
方法
通过实时 RT-PCR 和流式细胞术测量 pSS 患者、足癣和健康对照者的 CD4+T 细胞中的 CD70 水平。进行亚硫酸氢盐测序以确定 TNFSF7 启动子区域的甲基化状态。
结果
与对照组相比，pSS CD4+T 细胞中的 CD70 表达显著升高，并与 TNFSF7 启动子甲基化减少相关。
结论
CD70 启动子调节元件的去甲基化导致 pSS CD4+T 细胞中 CD70 的过度表达，并可能导致自身反应性。
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