白细胞介素-21在系统性红斑狼疮中的表达来源及与白细胞介素-17的相关性分析  

Expression, source and significance of interleukin-21 in patients with systemic lupus erythematosus and its correlation with interleuldn-17

作　　者：郑乐婷[1,2] 张磊[3] 赵丽丹[1] 赵铖[2] 刘升云[3] 赵岩[1] 张烜[1] 张奉春[1] 曾小峰[1] 唐福林[1] 尤欣[1] 

机构地区：[1]中国协和医科大学北京协和医院风湿免疫科,100032 [2]广西医科大学第一附属医院风湿免疫科 [3]郑州大学第一附属医院肾病风湿科

出　　处：《中华风湿病学杂志》2016年第12期801-805,I0001,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（30872333、81072404）;广西高等学校科学研究项目（KY2015LX062）;广西医科大学青年科学资助基金（GXMUYSF201335）

摘　　要：目的研究IL-21在初发SLE患者中的表达、来源及与IL-17的相关性。方法收集36例初发SLE患者和28名健康对照外周血标本，分离PBMCs及血清。流式细胞术检测PBMCs中CD4＋IL-21＋、CD4qL-17＋细胞比例；荧光定量PCR检测IL．21相关转录调节因子信号转导与转录激活因子3（STAT3）mRNA基因表达；ELISA检测SLE患者治疗前后血清IL-21水平；磁珠分选初治SLE患者CD4＋细胞，流式细胞术分选出CD4＋CD25＋细胞，检测IL-21在各T辅助细胞亚群Th1（CD4＋IFN-γ＋）、Th2（CD4＋IL4＋）、Th17（CD4＋IL-17＋）、滤泡T辅助细胞Tfh（CD4＋CXCR5＋）以及调节性T细胞（CD4＋CD25＋）上的表达。采用t检验和Pearson相关分析进行统计学分析。结果①SLE患者外周血CD4＋T细胞的IL-21表达水平[（10．0±5．9）％]显著高于健康对照[（4．4±1．8）％]（t=4．87，P〈0．01），且重型SLE[（14．3±5．4）％]显著高于轻型[（6．4±2．9）％]（t=4．90，P〈0．01）；②SLE患者血清IL．21水平[（317±27）pg/ml]较健康对照[（111±12）pg／ml]显著升高（t=5．60，P〈0．01），治疗后IL-21水平[（266±35）pg／m1]显著下降（t=11．6，P〈0．01）；③SLE患者PBMCs中STAT3mRNA水平（0．52±0．25）较健康对照组（0．32±0．12）显著上调（t=2．39，P〈0．05）；④Th1、Th2、Th17、Tfh及调节性T细胞均可分泌IL-21；⑤IL-21水平与SLEDAI评分、抗dsDNA抗体滴度及血清IgG呈正相关（r=0．634，19〈0．01；r=0．408，P〈0．05；r=0．585，P〈0．01），与补体c3呈负相关（r=-0．554，P〈0．05）；⑥SLE患者外周血CD4＋T细胞的IL-17表达水平及血清IL-17水平显著高于健康对照[（1．7±0．7）％和（1．0±0．5）％，t=3．04，P=0．006；（62±26）pg／ml和（41±15）pg／ml，t=2．92，P=0．015J，IL-21与IL-17水平呈正相关（r=0．488，P=0．029o结论SLE患者IL-21在SLE患者CD4＋T细胞表达异常升高，由调节性T细胞�Objective The expression and significance of interleukin （IL） -21 in patients with systemic lupus erythematosus （SLE） was studied and its correlation with IL-17 was explored. Methods Peripheral blood mononuclear cells （PBMCs） and serum were obtained from 36 patients with newly-onset SLE and 28 healthy controls. The frequency of CD4＋ T cells producing IL-21 and IL-17 were measured by flow cytometry. The expression of IL-21-associated transcriptor signal transducer and activator of transcription 3, signal transducer and activator, of tx＇anscription 3 （STAT3） mRNA was quantitatively measured ~by real-time polymerase chain reaction （RT-PCR）. The level of IL-21 in serum was detected by enzyme linked immunosorbent assay （ELISA） before and after 1 month treatment. CD4＋ cells from SLE patients were sorted by microbeads, and CD4＋CD25＋cells were sorted by flow cytometry, the frequency of CD4＋IL-21＋T, IL-21＋ Th1, IL-21＋Th2, IL- 21＋Th17, IL-21＋Treg and IL-21＋Tfh-like cells in peripheral blood were detected by flow cytometry; T-test and Pearson correlation analysis were used for statistical analysis. Results ① The percentages of IL-21＋ CD4＋T cells in PBMCs were significantly higher in SLE patients [（10.0±5.9）%] than healthy controls [（4.4±1.8）%] （t= 4.87, P〈0.01）, and IL-21 expression in severe SLE patients [（14.3±5.4）%] was significantly higher than that in mild SLE patients [（6.4±2.9）%] （t=4.90, P〈0.01）; ② Serum level of IL-21 in SLE patients [（317±27） pg/ml] was also significantly higher than human controls [（111±12） pg/ml] （t=5.60, P〈0.01）, and dropped rapidly after treatment [（266±35） pg/ml] （t=11.6, P〈0.01）. ③ The mRNA expression of STAT3 was significantly higher in SLE patients （0.52＋0.25） compared with HC （0.32±0.12） （t=2.39, P〈0.05）.④ IL-21 was produced broadly by Thl, Th2, Thl7, Tfh and Treg cells in SLE patients. ⑤ The expression of IL-21 on CD4＋T cells was positively correlate

关 键 词：红斑狼疮 系统性 白细胞介素21 白细胞介素17 T淋巴细胞 辅助诱导 

分 类 号：R593.241[医药卫生—内科学]