中华皮肤科杂志 ›› 2008, Vol. 41 ›› Issue (7): 439-442.

• 论著 • 上一篇    下一篇

SLE患者T淋巴细胞IL-13受体α1基因表达及其调节序列甲基化状态的研究

杨晓芹 陆前进 邱湘宁 等   

  1. 中南大学湘雅二医院皮肤性病科，中南大学湘雅二医院表观遗传学研究中心 中南大学湘雅二医院 长沙中南大学湘雅二医院皮肤性病科
  • 收稿日期:2007-08-31 修回日期:2008-03-16 发布日期:2008-07-15
  • 通讯作者: 杨晓芹 E-mail:incaicai@gmail.com

Expression and methylation status of IL-13 receptor α1 gene in peripheral T lymphocytes of patients with systemic lupus erythematosus

  • Received:2007-08-31 Revised:2008-03-16 Published:2008-07-15

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摘要：

目的 研究SLE患者外周血T淋巴细胞IL-13受体α1（IL-13Rα1）基因mRNA的表达及IL-13Rα1基因调节序列甲基化状态。方法 免疫磁珠法（MACS）分离10例SLE患者和6例正常人外周血CD4+和CD8+ T细胞，采用实时荧光定量PCR检测T细胞中IL-13Rα1 mRNA的表达，并用甲基化特异性PCR（MSP）方法检测IL-13Rα1基因调节序列的甲基化水平。结果 活动期SLE患者CD4+ T细胞中IL-13Rα1 mRNA表达水平为2.224 ± 0.251，非活动期SLE患者为1.712 ± 0.132，正常人组为1.104 ± 0.044，三组间比较，差异均有统计学意义（P < 0.05）；CD8+ T细胞中IL-13Rα1 mRNA表达水平活动期、非活动期及正常人组分别为1.672 ± 0.142，1.410 ± 0.154，1.238 ± 0.106，活动期组与正常人组比较差异有统计学意义（P < 0.05），而非活动期组与正常人组、活动期组与非活动期组比较，差异均无统计学意义（P > 0.05）。CD4+ T细胞中IL-13Rα1基因甲基化指数活动期SLE患者为0.454 ± 0.023，非活动期为0.635 ± 0.065，正常人为0.844 ± 0.097，三组间比较，差异均有统计学意义（P < 0.05）；CD8+ T细胞中IL-13Rα1基因甲基化指数三组间比较，差异均无统计学意义（P > 0.05）。SLE患者外周血CD4+，CD8+ T细胞IL-13Rα1 mRNA的表达与疾病活动度（SLEDAI评分）呈正相关（r = 0.79，P < 0.01；r = 0.76，P < 0.05）；CD4+ T细胞的IL-13Rα1基因的甲基化水平与疾病活动度（SLEDAI评分）呈负相关（r = -0.89，P < 0.01）；CD4+ T细胞IL-13Rα1 mRNA表达与其调节序列的甲基化水平呈负相关（r = -0.84，P < 0.01）。结论 SLE的发生发展可能与DNA低甲基化导致SLE患者T细胞过度表达IL-13Rα1有关。

关键词: 系统性红斑狼疮, IL-13R&alpha, 1, 甲基化, T细胞

Abstract:

Objective To investigate the mRNA expression and methylation status of IL-13 receptor （IL-13R） α1 gene in peripheral T lymphocytes of patients with systemic lupus erythematosus （SLE）. Methods Venous blood samples were obtained from 10 SLE patients （5 in active phase, 5 in inactive phase） and 6 normal human controls. CD4+ and CD8+ T cells were isolated from these samples via magnetic activated cell sorting （MACS）. Real-time quantitative PCR was used to test the mRNA expression of IL-13Rα1 gene, and methylation specific PCR to detect the methylation status. Results The expression level of IL-13Rα1 mRNA was 2.224 ± 0.251, 1.712 ± 0.132, and 1.104 ± 0.044 in CD4+ T cells of active SLE patients, inactive SLE patients and controls, respectively; the difference between the three groups was statistically significant（all P < 0.05）. The expression level of IL-13Rα1 mRNA in CD8+ T cells was significantly higher in active SLE patients than that in the normal controls （1.672 ± 0.142 vs 1.238 ± 0.106, P < 0.05）, while no difference was noted between inactive and active SLE patients or normal controls. The methylation index of IL-13Rα1 gene was 0.454 ± 0.023, 0.635 ± 0.065, 0.844 ± 0.097 in CD4+ T cells of active SLE patients, inactive SLE patients and normal controls, respectively, and the difference between the three groups was significant （all P < 0.05）, while no significant difference was observed in the methylation index in CD8+ T cells among these groups （P > 0.05）. The IL-13Rα1 mRNA expression in CD4+ T and CD8+ T cells was positively correlated with SLE disease activity index （SLEDAI） score （r = 0.79, 0.76, P = 0.007, 0.02 respectively）. A negative correlation was found between the methylation level of IL-13Rα1 in CD4+ T cells and SLEDAI score （r = -0.89, P < 0.01）, as well as between the IL-13Rα1 mRNA expression and its methylation level （r = -0.84, P < 0.01）. Conclusion The development of SLE may be related to the overexpression of IL-13Rα1 gene induced by DNA hypomethylation in T cells.

Key words: Systemic Lupus Erythematosus, IL-13R&alpha, 1, Methylation, T cells