桥本甲状腺炎患者外周血调节性T细胞/Th17细胞平衡动态变化的研究

目的 探讨桥本甲状腺炎(HT)患者外周血调节性T细胞(Treg)与Th17细胞的动态变化及其意义.方法 流式细胞术检测36例HT患者和30例健康对照者外周血单个核细胞(PBMC)中Treg和Th17细胞的比例,实时定量RT-PCR检测Treg和Th17细胞特异性转录因子Foxp3、RORγt mRNA的表达水平,ELISA检测血清中相关细胞因子TGF-β和IL-17A的含量.结果 HT患者PBMC中Treg细胞比例及Foxp3 mRNA表达水平均明显低于健康对照者(t=-10.62、-7.624,P均<0.01),HT亚组间差异具有统计学意义(F=4.414、4.512,P均<0.05);Th17细胞比例、RORγt mRNA表达水平及Th17/Treg比值均明显高于健康对照者(t=11.32、19.25、8.386,P均<0.01),HT亚组间差异均具有统计学意义(F分别为34.947、14.551、24.338,P均<0.01),亚组间两两比较差异均有统计学意义(P均<0.05).HT患者血清TGF-β的含量较健康对照者略低,但差异无统计学意义(P>0.05);IL-17A的含量均较健康对照者显著升高(P<0.01),HT患者组内各亚组间血清IL-17A的含量差异具有统计学意义(F=11.077,P<0.01),两两比较差异亦具有统计学意义(P均<0.05).HT患者Th17/Treg比值与血清甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)滴度均呈显著正相关(r=0.349、0.502,P=0.037、0.002).结论 在HT发病过程中,Th17/Treg细胞轴呈动态改变,并且与甲状腺自身抗体滴度正相关,说明Th17/Treg细胞亚群的免疫失平衡可能参与了HT的发生发展.

The dynamic changes of Treg/Thl7 cells imbalance in patients with Hashimoto thyroiditis

Objective To investigate the dynamic changes and significance of regulatory T cells（Treg）and Thl7 cells in patients with Hashimoto thyroiditis （HT）. Methods 36 HT patients 18 cases with euthyroidism （subset A）, 10 cases with subclinical hypothyroidism（ subset B） ,8 cases with overt hypothyroidism（ subset C）] and 30 healthy controls（NC）were selected. Flow cytometry was performed to detect the percentages of Treg and Thl7 cells. Real-time RT-PCR was employed to analyze the expressions of Foxp3 and RORγt mRNA. Serum concentrations of TGF-13 and IL-17A were measured by ELISA. Results Treg ceils percentages and Foxp3 mRNA levels decreased obviously in HT patients（ t = - 10. 62, -7. 624 respectively and both P 〈 0. 01 ）, one-way ANOVA test in A, B and C subsets revealed that the differences were significant （ F = 4.414,4. 512 respectively and both P 〈 0.05 ）, and a significant increase in Thl7 cells percentages, ROR~/t mRNA levels and the ratio of Thl7/Treg cells （t = 11.32, 19. 25,8. 386 respectively and all P 〈 O. 01 ）compared with NC, one-way ANOVA test in A, B and C subsets revealed that the differences were significant （ F = 34. 947, 14. 551,24. 338 respectively and all P 〈 0.01 ）, and multiple comparison in A, B and C subsets revealed that the differences were significant （ all P 〈 0. 05 ）. There was no statistical difference in serum concentration of TGF-I3 between HT and NC （P 〉 0. 05 ）, while IL-17A levels increased markedly in HT patients（ P 〈 0. 01 ）. In HT patients, the ratio of Th17/Treg ceils positively correlated with the levels of serum thyroperoixidase antibody （ TPOAb）, thyroglobulin antibody （ TgAb ） （ r = 0. 349,0. 502 and P = 0. 037, 0. 002 respectively）. Conclusions During the process of HT, there were dynamic changes of Thl7/Treg cells, and positively correlated with the thyroid specific autoantibodies,which may lead to immune imbalance and contribute to the development of HT.