中文摘要：

目的探讨IL-6／STAT3信号在川崎病（KD）Th17／Tr细胞失衡中的作用。方法急性期KD患儿48例，正常同年龄对照组18例，KD患儿于静脉注射丙种球蛋白前直接取血备检。酶联免疫吸附试验（ELISA）检测血浆IL-6蛋白浓度；荧光定量PCR检测CD4^＋T细胞IL-17A、IL．17F、RORγt、Foxp3、SOCSl、SOCS3等基因mRNA表达；流式细胞术检测外周血CD4^＋CD25^＋Foxp3^＋调节性T细胞（Tr）的比例和CD4^＋T细胞磷酸化STAT3（pSTAT3）蛋白平均荧光强度（MFI）；甲基化特异性定量PCR（MethySYBRPCR）检测CD4^＋T细胞SOCSl基因外显子2、SOCS3基因5^＋端非翻译区（5＇-UTR）3个可能的STAT3结合位点CpG岛甲基化水平。结果（1）急性期KD患儿血浆IL-6浓度、CD4^＋T细胞pSTAT3MFI水平显著上调[IL-6：（54．02±20．58）pg／mlvs（8．72±2．06）pg／ml，P〈0．05；pSTAT3MFI：（55．41＋15．08）VS（9．35＋3．76），P〈0．05]。其中KD合并冠脉损伤组（KD-CAL^＋）上述二项指标均明显高于无冠脉损伤组（KD—CAL一）[IL-6：（84．76±29．35）pg／mlVS（38．65±13．76）pg／ml，P〈0．05；pSTAT3MFIt（72．36＋16．81）VS（46．93±13．57），P〈0．05]。（2）急性期KD患儿CD4^＋T细胞IL-17A／F、RORTtmRNA表达水平显著上调（P〈0．05），CD4^＋CD25^＋Foxp3^＋Tr细胞比例及Foxp3mRNA表达明显低于正常对照组（P〈0．05），其中KD．CAL^＋组IL一17A／F、ROR,／tmRNA表达水平明显高于KD—CAL一组（P〈0．05），roxp3mRNA表达明显低于KD—CAL一组（P〈0．05）。（3）急性期KD患儿CD4^＋T细胞SOCSl和SOCS3mRNA水平显著高于同年龄对照组（P〈0．05），其中KD-CAL^＋组SOCSl和SOCS3mRNA表达低于KD—CAL-组（P〈0．05）；正常对照组SOCSl基因外显子2、SOCS3基因5^＋-UTR区第3个STAT3结合位点的CpG岛完全去甲基化，急性期KD患儿呈低甲基化状态（P〈0．05），其中KD-CAL^＋组SOCSl基因外显子2、SOCS3基因5^＋-

英文摘要：

Objective To investigate the role of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease（KD）. Methods Forty-eight children with KD and eighteen age-matched healthy children were consented to participate in this study. Protein concentration of IL-6 in plasma was measured by ELISA. Transcriptional levels of IL-17A, IL-17F, RORTt, Foxp3, SOCS1 and SOCS3 were assessed by real-time PCR. The proportion of CD^＋ CD25^＋ Foxp3± regulatory T （Tr） cells and mean fluorescence intensity （MFI） for phosphorylated-STAT3 （pSTAT3） protein in CD4＋ T cells was analyzed by flow cytometry. A quantitative methylation specific PCR based on SYBR Green was used to evaluate methylation status of CpG islands in SOCS1 exon2, three potential bind sites for STAT3 in 5＇-untraslated region （5＇-UTR） of SOCS3 in CD4 T cells. Results （1）Compared with healthy volunteers, plasma IL-6 concentration and MFI for pSTAT3 in CD± T cells were elevated significantly during acute phase of KD[ IL-6： （54.02±20.58） pg/ml vs （8.72± 2.06） pg/ml, P〈0.05 ; pSTA33 MFI： （55.41±15.08） vs （9.35±3.76）, P〈0.051, and the two items in KD patients with coronary artery lesion （ KD-CAL ） were found to be higher than those in KD patients without coronary artery lesion （ KD-CAL- ） [ IL-6 ： （ 84.76±29.35 ） pg/ml vs （ 38.65 ± 13.76） pg/ml, P〈0.05 ; pSTAT3 MFI： （72.36±16.81） vs （46.93±13.57）, P〈0.05 ]. （2） Transcription levels of IL-17A, IL-17F and RORγt in patients with KD were significantly elevated （P〈0. 05 ） while the proportion of CD± CD25± Foxp3± Treg and expression levels of Foxp3 were detected to be lower than those in normal controls （ P〈0. 05）. The mRNA levels of IL-17A, IL-17F and RORγt in KD-CAL± group were higher than those in KD- CAL- group（P〈0.05）, as well as expression level of Foxp3 were found to be lower in KD-CAL± group（P〈0. 05）. （3） The mRNA levels of SOCS1 and SOCS3 in CD4± T cells increased significantly during a