Shenzhen Institute of Pediatrics, Shenzhen Children Hospital, Chongqing University of Medical Sciences, Shenzhen, China.
Clin Exp Immunol. 2010 Oct;162(1):131-7. doi: 10.1111/j.1365-2249.2010.04236.x. Epub 2010 Aug 16.
The study is designed to investigate the changes and roles of T helper type 17/regulatory T cells (Th17/T(reg) ) 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(+) FoxP3(high) T(regs) 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 T(reg) proportions and expression levels of T(reg ) 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/T(reg) 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.
本研究旨在探讨辅助性 T 细胞 17/调节性 T 细胞(Th17/Treg)在川崎病(KD)免疫发病机制中的变化和作用。此外,我们还探讨了静脉注射免疫球蛋白(IVIG)耐药性 KD 患者中 Th17 细胞的改变及其意义。采用实时聚合酶链反应(PCR)检测 CD4阳性细胞中白细胞介素(IL)-17A/F、维甲酸相关孤儿受体(ROR)-γt 和叉头框 P3(FoxP3)的 mRNA 水平。采用流式细胞术分析 Th17 细胞和 CD4+CD25+FoxP3+T 调节细胞(Treg)的比例。采用夹心酶联免疫吸附试验测定血浆细胞因子[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)及转录因子(IL-17A/F、ROR-γt)的表达水平显著上调,而 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,免疫球蛋白耐药性 KD 患者急性期 Th17 比例显著上调(P<0·01)。KD 患者的血浆 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(ID)组(P<0·05)。KD 组血浆 TGF-β浓度明显低于 NC 组和 ID 组(P<0·05)。这些结果表明,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导致免疫球蛋白耐药性 KD 的重要因素。