IL-21上调IL-17的表达在Graves病中的意义

Significance of IL-17 upregulation by IL-21 in patients with Graves disease

目的探讨IL-21上调IL-17表达在Graves病(GD)中的意义。方法收集30例初发GD患者、17例经药物治疗后甲状腺功能恢复正常的GD(eGD)患者和18例健康对照者,采用电化学发光法检测患者的甲状腺功能指标(FT3、FT4和uTSH)和自身抗体(TgAb、TPOAb和TRAb)水平。采集研究对象的外周血并分离单个核淋巴细胞(PBMCs),设IL-21刺激组和IL-21未刺激组。体外培养PBMCs后,ELISA法检测细胞上清液中IL-17蛋白的表达;半定量RT-PCR法检测IL-17和RORγt mRNA的表达。结果 GD组的甲状腺功能指标与正常对照组eGD组比较,差异均有统计学意义(P<0.05);但eGD组与正常对照组比较差异无统计学意义(P>0.05)。GD组和eGD组的自身抗体水平均显著高于正常对照组,差异有统计学意义(P<0.05);但GD组与eGD组比较差异无统计学意义(P>0.05)。IL-21刺激前,GD组、eGD组的IL-17 mRNA、RORγt mRNA和IL-17蛋白表达水平均较正常对照组明显升高,差异有统计学意义(P<0.05),但GD组与eGD组比较差异无统计学意义(P>0.05)。经IL-21刺激后,GD组、eGD组和正常对照组的IL-17 mRNA、RORγt mRNA和IL-17蛋白的表达水平均显著高于刺激前,且GD组和eGD组显著高于正常对照组,差异均有统计学意义(P<0.05);但GD组与eGD组间比较差异无统计学意义(P>0.05)。结论 IL-21通过上调IL-17的表达参与了GD的发病机制,且这一机制可能并不依赖于甲状腺功能,而与自身免疫过程相关。

Objective To analyze the role of IL-21 in IL-17 upregulation of patients with Graves disease （GD）. Methods Thirty patients with GD were enrolled as GD group; 17 patients with euthyroid GD after treatment, as eGD group; and 18 healthy subjects, as control group. Electrochemical luminescence detection was used to determine levels of thyroid function indexes （FT3, FT4, and uTSH） and autoantibodies （TgAb, TPOAb, and TRAb）. The peripheral blood mononuclear cells （PBMCs） were cultured in the presence or absence of IL-21 in vitro. The level of IL-17 protein was measured by enzyme- linked immunosorbent assay （ELISA）, and expressions of IL-17 and ROR＇,/t mRNA were examined by semi-quantitative RT-PCR. Results Compared to control and eGD groups, there were significantly differences in the levels of thyroid function indexes in GD group （P 〈 0.05）, whereas there was no difference between control group and eGD group （P 〉 O. 05）. Before IL-12 stimulation, compared to control group, expressions of IL-17 and ROR＂yt mRNA and level of IL-17 protein were significantly higher in GD and eGD groups （ P 〈 0.05） ; but there were no significant differences between GD group and eGD group （P 〉 0.05）. After IL-12 stimulation, expressions of IL-17 and ROR~/t mRNA and IL-17 protein levels markedly increased in all three groups, which were significantly higher in GD and eGD groups compared to control group （P 〈 0. 05）. There were no differences of the values between GD group and eGD group （P 〉 0. 05）. Conclusion The results indicated that IL-21 involved in the pathogenesis of GD through IL-17 upregulation, which might be not dependent on thyroid function but be related to autoimmunity.