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目的:观察白细胞介素-35(IL-35)在桥本甲状腺炎(HT)中的表达，评估IL-35对HT患者调节性T细胞(Treg)和辅助性T细胞22(Th22)平衡的调控。方法:连续入组HT患者42例和对照者18名，分离血浆和外周血单个核细胞(PBMC)，分选Treg。酶联免疫吸附试验检测血浆IL-35和IL-22，流式细胞术检测Treg和Th22比例，实时定量PCR法检测叉头框蛋白3(FoxP3)和芳香烃受体(AhR)mRNA表达。使用IL-35刺激Treg后与自体PBMC共培养，并诱导Treg向Th22表型转分化，评估IL-35对HT患者Treg功能和转分化的影响。结果:HT组Treg和Th22存在失衡，Treg比例、FoxP3 mRNA、血浆IL-35低于对照组( P<0.001)，Th22比例、AhR mRNA高于对照组( P<0.001)，血浆IL-22水平在2组间差异无统计学意义( P＝0.775)。HT组Treg抑制细胞增殖能力减弱( P＝0.013)，IL-35和IL-10分泌低于对照组( P<0.001)。HT组Treg向Th22细胞表型转分化能力升高，CCR4、CCR6和CCR10表达、AhR mRNA、IL-22分泌高于对照组( P<0.01)。IL-35刺激HT组PBMC可导致Treg比例、FoxP3 mRNA、IL-35和IL-10分泌升高( P<0.05)，但对Th22比例、AhR mRNA、IL-22分泌无影响( P>0.05)。IL-35刺激增强HT组Treg功能，抑制细胞增殖能力增强、IL-35和IL-10分泌增加( P<0.05)。IL-35刺激降低HT组Treg向Th22表型转分化，CCR4、CCR6和CCR10表达、AhR mRNA、IL-22分泌降低( P<0.05)。 结论:IL-35增强HT患者Treg免疫抑制功能、抑制Treg向Th22表型转分化，调控Treg与Th22细胞平衡。

Objective:To observe the expression of interleukin-35(IL-35) in Hashimoto's thyroiditis(HT) patients, and evaluate its regulatory effect on the balance between regulatory T cells(Treg) and T helper 22(Th22) cells.Methods:Forty-two HT patients and eighteen controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMC) were isolated. Treg were purified. Plasma IL-35 and IL-22 were detected with enzyme-linked immunosorbent assay. Treg and Th22 percentages were measured using flow cytometry. Real-time quantitative PCR was used to assess mRNA levels of forhead box protein 3(FoxP3) and aryl hydrocarbon receptor(AhR). Treg were stimulated with exogenous IL-35, and were co-cultured with autologous PBMC to induce Treg-to-Th22 phenotypic differentiation, evaluating the effect of IL-35 on Treg function and differentiation.Results:There was imbalance between Treg and Th22 cells in HT group. HT group had reduced Treg percentage, plasma IL-35 and FoxP3 mRNA( P<0.001), while had elevated Th22 percentage and AhR mRNA( P<0.001). There was no significant difference in plasma IL-22 level between two groups( P=0.775). The suppressive capacity of Tregs in the HT group was diminished( P=0.013), and secretion levels of IL-35 and IL-10 were lower than those in the control group( P<0.001). The ability of Tregs in the HT group to differentiate into Th22 cells was increased, with higher levels of CCR4, CCR6, CCR10, AhR mRNA, and IL-22 secretion compared to the control group( P<0.01). IL-35 stimulation induced elevation of Treg percentage, FoxP3 mRNA, and IL-35/IL-10 secretion( P<0.05), but did not affect Th22 percentage, AhR mRNA, or IL-22 secretion( P>0.05). IL-35 stimulation enhanced Treg function in HT group, increasing proliferation inhibition and secretion of IL-35 and IL-10( P<0.05). IL-35 stimulation reduced the differentiation of Treg to Th22 phenotype in HT group, with decreased levels of CCR4, CCR6 CCR10, AhR mRNA, and IL-22 secretion( P<0.05). Conclusion:IL-35 enhances the immunosuppression of Tregs in HT patients and inhibits its differentiation into Th22 cells, thus regulating the balance between Tregs and Th22 cells.