IL-4通过促进CD30分子表达抑制类风湿关节炎患者T细胞功能的研究  

IL-4 inhibits T cell function in patients with rheumatoid arthritis through promoting CD30 expression

作　　者：李伟[1] 王佳怡[1] 肖春媛[1] 陆天琳 黄新芳 韩捷[1] LI Wei;WANG Jia-yi;XIAO Chun-yuan;LU Tian-lin;HUANG Xin-fang;HAN Jie(Dept.of Rheumatology,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200120,China)

机构地区：[1]同济大学附属东方医院风湿免疫科,上海200120

出　　处：《同济大学学报（医学版）》2021年第4期528-533,共6页Journal of Tongji University(Medical Science)

基　　金：上海市浦东新区科委创新基金(PKJ2016-Y61);同济大学中央高校基本科研项目(22120180467)。

摘　　要：目的观察IL-4和CD30在类风湿关节炎(rheumatoid arthritis,RA)中的潜在关联,并探讨其对T细胞促炎细胞因子分泌的影响。方法选取46例活动期RA患者(RA组)及41例健康人(对照组)为研究对象,其中RA患者DAS28评分3.89~7.41分,平均(4.23±1.42)分。ELISA法测定RA血清中IL-4和sCD30含量并分析二者相关性;流式细胞术分析重组人TIL-4蛋白对PBMC来源的T细胞表面CD30表达的影响,观察IL-4刺激后CD30+T及CD30-细胞内IFN-γ、IL-17的水平变化。结果与健康对照组相比,RA患者血清中sCD30水平显著升高(P<0.0001),IL-4水平也有升高(P<0.01),Pearson相关性分析显示二者存在正相关。在抗CD3、抗CD28活化培养条件下,重组IL-4蛋白可促进RA患者外周血中T细胞表达CD30分子增加,增加程度与IL-4浓度呈正比。细胞内荧光染色显示,RA患者CD30+T细胞内IL-17较对照组明显升高(P<0.05)。重组IL-4蛋白能降低RA及对照组外周血中CD30+T细胞分泌IFN-γ、IL-17,而对CD30-T细胞内细胞因子的分泌无明显影响。结论IL-4可能通过促进T细胞上CD30分子表达降低促炎细胞因子产生,在RA中发挥免疫调节作用。Objective To investigate the potential association of IL-4 and CD30 in rheumatoid arthritis and to explore their effects on T cell pro-inflammatory cytokine secretion.Methods Forty-six active RA patients with an average DAS28 score of 4.23±1.42(3.89-7.41)(RA group)and forty-one healthy subjects(control group)were enrolled in the study.The serum levels of IL-4 and sCD30 were measured by ELISA,the expression of CD30 on T cells derived from PBMC was analyzed by flow cytometry,the levels of IFN-γand IL-17 in CD30+T cells and CD30-T cells were determined after IL-4 stimulation.Results Compared with the control group,the serum sCD30 and IL-4 levels in RA patients were significantly increased(P<0.0001 and P<0.01).Pearson correlation analysis showed that there was a positive correlation between them.Under the stimulation of anti-CD3 and anti-CD28,recombinant human IL-4 protein significantly increased the expression of CD30 on T cells of RA patients in a dose-dependent manner(P<0.05).Intracellular fluorescence staining showed that IL-17 in CD30+T cells of RA patients was significantly higher than that in healthy controls(P<0.05).IL-4 decreased the secretion of IFN-γand IL-17 by CD30+T cells in RA and control group but had no effect on CD30-T cells.Conclusion IL-4 may play an immunomodulatory role in RA by promoting the expression of CD30 on T cells and decreasing the production of pro-inflammatory cytokines.

关 键 词：白细胞介素-4 CD30分子 类风湿关节炎 T细胞 

分 类 号：R593.22[医药卫生—内科学]