系统性红斑狼疮患者外周血初始CD4^(+)T细胞转化生长因子-β受体Ⅰ水平的变化和临床意义  

The clinical significance of the transforming growth factor-βreceptor I expression in naïve CD4^(+)T cells from patients with systemic lupus erythematosus

作　　者：严青 龙现明[1] 赵盛楠 宋骅 陈纬纬 林禾[2] 孙凌云 Yan Qing;Long Xianming;Zhao Shengnan;Song Hua;Chen Weiwei;Lin He;Sun Lingyun(Department of Rheumatology and Immunology,Drum Tower Clinical Medical College of Nanjing Medical University,Nanjing 210008,China;Department of Rheumatology and Immunology,Shengli Clinical Medical College of Fujian Medical University,Fuzhou 350001,China)

机构地区：[1]南京医科大学鼓楼临床医学院风湿免疫科,210008 [2]福建医科大学省立临床医学院风湿免疫科,福州350001

出　　处：《中华风湿病学杂志》2021年第10期649-653,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金面上项目(81771677);国家自然科学基金重点国际(地区)合作研究项目(81720108020);国家自然科学基金重点项目(81930043);福建省自然科学基金面上项目(2019J01183)。

摘　　要：目的探讨SLE患者外周血初始CD4^(+)T细胞的TGF-β受体Ⅰ(TGF-βRⅠ)mRNA表达水平和疾病活动的相关性。方法磁珠分选法分离纯化SLE患者及健康对照组外周血单个核细胞中的初始CD4^(+)T细胞,实时定量PCR法检测初始CD4^(+)T细胞的TGF-βRⅠmRNA水平,流式细胞术检测CD4^(+)T细胞中CD69阳性细胞的百分率。采用t检验及Pearson相关性分析统计数据。结果SLE患者初始CD4^(+)T细胞的TGF-βRⅠmRNA水平显著低于健康对照组[(0.674±0.873)与(1.445±1.112),t=2.301,P<0.05]。SLE患者初始CD4^(+)T细胞的TGF-βRⅠmRNA水平与SLEDAI评分(r=-0.376,P<0.05),ESR(r=-0.376,P<0.05)、血清肌酐(r=-0.323,P<0.05)和尿蛋白定量(24 h)(r=-0.331,P<0.05)均呈负相关,与血清补体C3(r=0.528,P=0.001)呈正相关。累及肾脏的SLE患者初始CD4^(+)T细胞的TGF-βRⅠmRNA水平较未累及肾脏的SLE患者更低[(0.505±0.536)与(1.071±1.007),t=2.198,P<0.05]。血清抗dsDNA抗体阳性组初始CD4^(+)T细胞的TGF-βRⅠmRNA水平较抗dsDNA抗体阴性组水平低[(0.344±0.315)与(0.958±1.076),t=2.277,P<0.05]。体外实验中,SLE患者初始CD4^(+)T细胞活化后TGF-βRⅠmRNA表达水平显著降低[(0.047±0.013)与(1.008±0.129),t=14.38,P<0.01],地塞米松可上调活化的CD4^(+)T细胞TGF-βRⅠmRNA表达水平[(0.240±0.042)与(0.047±0.013),t=7.845,P<0.01],同时地塞米松可显著下调CD4^(+)T细胞的CD69表达水平[(15.0±2.1)%与(34.9±2.0)%,t=32.57,P<0.01]。结论SLE患者初始CD4^(+)T细胞的TGF-βRⅠ低表达可能参与了SLE疾病的发生发展,糖皮质激素治疗可上调初始CD4^(+)T细胞的TGF-βRⅠmRNA水平,靶向TGF-βRⅠ可能成为治疗SLE的新方法。Objective To investigate the clinical significance of the transforming growth factor-βreceptor I(TGF-βRⅠ)expression in naïve CD4^(+)T cells from patients with systemic lupus erythematosus(SLE).Methods Naïve CD4^(+)T cells were purified using magnetic microbeads from peripheral blood mononuclear cells of SLE patients and healthy controls.Real-time quantitative PCR was used to detect TGF-βRⅠmRNA level,and flow cytometry was used to detect the percentage of CD69+CD4^(+)T cells.Data were analyzed by t test and Pearson correlation analysis.Results The level of TGF-βRⅠmRNA in naïve CD4^(+)T cells from SLE patients was significantly lower than that in healthy controls[(0.674±0.873)vs(1.445±1.112),t=2.301,P<0.05].The TGF-βRⅠmRNA level was negatively correlated with systemic lupus erythematosus disease activity index(SLEDAI)(r=-0.376,P<0.05),erythrocyte sedimentation rate(ESR)(r=-0.376,P<0.05),serum creatinine(r=-0.323,P<0.05)and 24 h urine protein(r=-0.331,P<0.05),and positively correlated with serum com-plement C3(r=0.528,P<0.01).The level of TGF-βRⅠmRNA level in naïve CD4^(+)T cells in SLE patients with renal involvement was lower than that in SLE patients without renal involvement[(0.525±0.536)vs(1.071±1.007),t=2.198,P<0.05].The TGF-βRⅠmRNA level in the naïve CD4^(+)T cells in anti-dsDNA antibody positive group was lower than that in the anti-dsDNA antibody negative group[(0.344±0.315)vs(0.958±1.076),t=2.277,P<0.05].The expression of TGF-βRⅠmRNA in naïve CD4^(+)T cells from SLE patients was reduced after 24 h stimulation with anti-CD3/CD28 beads[(0.047±0.013)vs(1.008±0.129),t=14.38,P<0.01],which was partially reversed by dexamethasone treatment[(0.240±0.042)vs(0.047±0.013),t=7.845,P<0.01].Meanwhile,dexamethasone significantly decreased the expression of CD69 in CD4^(+)T cells[(15.0±2.1)%vs(34.9±2.0)%,t=32.57,P<0.01].Conclusion The abnormally low expression of TGF-βRⅠin naïve CD4^(+)T cells may be involved in the pathogenesis of SLE.Glucocorticoid treatment can upregulate the

关 键 词：红斑狼疮 系统性 受体 转化生长因子-β T细胞活化 

分 类 号：R593.241[医药卫生—内科学]