The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease
The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease
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急性川崎病患者17型辅助T细胞/调节性T细胞失衡
DOI：
10.1111/j.1365-2249.2010.04236.x
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发表时间：
2010-10-01
影响因子：
4.6
通讯作者：
Zu, Y.
中科院分区：
文献类型：
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作者：
Jia, S.;Li, C.;Zu, Y.
本研究旨在探讨辅助性T型17/调节性T细胞（Th17/Treg）在川崎病（Kawasaki disease， KD）免疫发病机制中的变化及其作用。此外，我们探讨了Th17细胞在静脉免疫球蛋白抵抗性KD患者中的改变及其意义。采用实时聚合酶链反应（Real - time polymerase chain reaction， PCR）检测CD4阳性细胞中白细胞介素（IL）‐17A/F、视黄酸相关孤儿受体（ROR）‐γ - t和叉头盒P3 (FoxP3) mRNA水平。流式细胞术分析Th17细胞和CD4+CD25+ foxp3高treg的比例。采用三明治酶联免疫吸附法测定血浆细胞因子[IL‐17A、IL‐6、IL‐23和转化生长因子（TGF）‐β]浓度。我们的数据表明，急性KD患儿Th17比例和细胞因子（IL‐17、IL‐6和IL‐23）和转录因子（IL‐17A/F、ROR‐γt）的表达水平显著上调，Treg比例和Treg转录因子（FoxP3）的表达水平显著下调（P < 0.01）。与敏感组相比，免疫球蛋白耐药KD急性期Th17比例显著上调（P < 0.01）。KD患者血浆IL - 17A、IL - 6和IL - 23浓度明显高于正常对照组（NC）和感染性疾病组（ID）。KD组大鼠血浆TGF - β浓度显著低于NC和ID组（P < 0.05）。这些结果提示KD患者存在Th17/Treg细胞失衡。Th17/T细胞失衡可能是导致免疫功能紊乱和免疫球蛋白抵抗性KD的重要因素。
The study is designed to investigate the changes and roles of T helper type 17/regulatory T cells (Th17/Treg) in the immunological pathogenesis of Kawasaki disease (KD). In addition, we explore the alteration and significance of Th17 cells in patients with intravenous immune globulin‐resistant KD. Real‐time polymerase chain reaction (PCR) was used to evaluate the mRNA levels of interleukin (IL)‐17A/F, retinoic acid‐related orphan receptor (ROR)‐γt and forkhead box P3 (FoxP3) in CD4‐positive cells. The proportions of Th17 cells and CD4+CD25+FoxP3high Tregs were analysed by flow cytometry. Plasma cytokine [IL‐17A, IL‐6, IL‐23 and transforming growth factor (TGF)‐β] concentrations were measured by sandwich enzyme‐linked immunosorbent assay. Our data demonstrate that Th17 proportions and expression levels of cytokines (IL‐17, IL‐6 and IL‐23) and transcription factors (IL‐17A/F, ROR‐γt) were up‐regulated significantly, while Treg proportions and expression levels of Treg transcription factor (FoxP3) were down‐regulated significantly in children with acute KD (P < 0·01). Compared with the sensitive group, the Th17 proportions were up‐regulated significantly during the acute phase in immune globulin‐resistant KD (P < 0·01). The plasma IL‐17A, IL‐6 and IL‐23 concentrations in patients with KD were significantly higher compared with the concentrations in normal controls (NC) and infectious disease (ID). Plasma TGF‐β concentrations were markedly lower in the KD group than the NC and ID groups (P < 0·05). These results suggest that Th17/Treg cells imbalance exists in the patients with KD. Th17/T cells imbalance may be important factors causing disturbed immunological function and resulting in immunoglobulin‐resistant KD.