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转录因子T-bet、GATA-3、FoxP3及CD4~+CD25~+调节性T细胞在儿童过敏性紫癜发病机制中的作用

Effects of Transcription Factor T-bet,GATA-3,FoxP3 and CD4~+CD25~+ Regulatory T Cells in Pathogenesis of Child Hench-Schonlein Purpura

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【作者】 王强任淑红董巍房俊

【Author】 WANG Qiang,REN Shu-Hong,DONG Wei1,FANG Jun1 Department of Pediatrics;1Center of Clinical Experimental Medicine,Sichuan Province People Hospital,Chengdu 610072,Sichuan Province,China

【机构】 四川省人民医院儿科郑州市第一人民医院儿科四川省人民医院临床医学中心实验室

【摘要】 本研究旨在探讨转录因子T-bet、GATA-3和CD4+CD25+调节性T细胞及其转录因子FoxP3在儿童过敏性紫癜(HSP)发病机制中的作用。2009年2月-2010年2月在本院收治的46例急性期HSP患儿(HSP组)及30例健康对照儿童(对照组)纳入研究。采用SYBR GreenⅠ实时荧光定量PCR方法检测外周血单个核细胞T-bet、GATA-3及FoxP3 mRNA的表达。运用流式细胞术检测外周血中T淋巴细胞亚群CD4+CD25+的表达。结果表明,HSP组患儿GATA-3 mRNA相对表达水平(964.30±655.18)显著高于对照组儿童GATA-3 mRNA相对表达水平(78.09±57.20,P<0.01)。HSP组患儿T-bet mRNA(53.98±35.79)、FoxP3 mRNA(32.17±23.04)和CD4+CD25+(5.34±2.51)相对表达水平低于对照组儿童T-bet mRNA(181.56±96.90)、FoxP3 mRNA(147.91±99.15)和CD4+CD25+(7.85±1.97)相对表达水平(P<0.01)。结论:HSP患儿急性期存在Th1特异性转录因子T-betmRNA表达下调,Th2特异性转录因子GATA-3 mRNA表达上调。HSP患儿急性期存在CD4+CD25+调节性T细胞及其特异性转录因子FoxP3 mRNA表达下调,调节性T细胞的减少及由此引发的免疫抑制效应不足可能是HSP急性期免疫失衡的重要原因之一。本研究为从调节性T细胞及其调控的分子机制角度进一步阐明儿童HSP的发病机制提供了实验依据。

【Abstract】 The aim of this study was to investigate the effects of transcription factors T-bet,GATA-3 in the pathogenesis of Hench-Schonlein purpura(HSP) in children,the relationship between CD4+CD25+regulatory T cells,transcription factor FoxP3 and the development of child HSP,and the molecular mechanisms of Th1/Th2 imbalance of child HSP at acute phase,so as to may provide a new approach and strategy for the treatment of HSP at the molecular levels.The expression of T-bet,GATA-3 and FoxP3 mRNA were detected by real time PCR using SYBR Green Ⅰ in 46 patients with HSP at acute phase and 30 healthy childran as controls. The expression of T lymphocyte subsets CD4+CD25+ in peripheral blood mononuclear cells was detected by flow cytometry.The results showed that the relative level of GATA-3 mRNA in peripheral blood mononuclear cells of patients with HSP was significantly higher than those of the control group(964.30±655.18 vs 78.09±57.20,P<0.01).The relative level of T-bet mRNA in peripheral blood mononuclear cells of patients with HSP was lower than those of the control group(53.98±35.79 vs 181.56±96.90,P<0.01).The expression level of FoxP3 mRNA with HSP was lower than that of the control group(32.17±23.04 vs 147.91±99.15,P<0.01).The result of CD4+CD25+ Treg with HSP was lower than those of the control group((5.34±2.51)% vs(7.85±1.97)%,P<0.01)).It is concluded that Th1/Th2 imbalance exists in acute phase of child HSP,especially predominant activation of Th2,which correlates with the abnormal expression of transcription factor T-bet and GATA-3 mRNA.At acute phase of child HSP,the expression of CD4+CD25+Treg and its special transcription factor FoxP3 mRNA are down-regulated.Treg cells decreases,which indicates that insufficient immunosuppressive effects resulting from the reduction of Treg cells may be one of the important reason in the immune imbalance of HSP acute phase.This study provides experimental evidence for illustrating the pathogenesis of HSP from the molecular mechanism of Treg cells and its regulation,and also provides a new thinking and new strategies for the treatment of HSP at molecular levels.

【基金】 四川省卫生厅科研课题(编号303005002209044)
  • 【文献出处】 中国实验血液学杂志 ,Journal of Experimental Hematology , 编辑部邮箱 ,2012年01期
  • 【分类号】R725.5
  • 【被引频次】25
  • 【下载频次】288
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