白细胞介素-21及地塞米松对系统性红斑狼疮患者滤泡辅助性T细胞表达的影响  

Effect of interleukin-21 and dexamethasone on follicular helper T cells in patients with systemic lupus erythematosus

作　　者：陈京京[1] 王丹丹[2] 刘蕊[2] 李霞[2] 冯学兵[2] 孙凌云[2] 

机构地区：[1]中国医学科学院中国协和医科大学皮肤病研究所过敏免疫科,南京210042 [2]南京大学医学院附属鼓楼医院风湿免疫科

出　　处：《中华风湿病学杂志》2013年第10期657-660,I0001,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（81172846）;江苏省医学重点人才项目;南京市医学科技发展项目（YKK10079）

摘　　要：目的通过体外实验观察白细胞介素（IL）-21及地塞米松对系统性红斑狼疮（SLE）患者滤泡辅助性T细胞（Tfh）表达的调控作用并初步探讨其可能的机制。方法收集11例SLE患者外周血，将分离出的单个核细胞（PBMCs）按10s个，孔置入96孔培养板，分对照组、重组人白细胞介素（rIL）-21组及rIL-21±地塞米松组（rIL-21浓度为200ng／μl、地塞米松浓度为1×10-6mol／L）体外分别培养24、72h；另分离20例SLE患者PBMCs，分对照组及地塞米松组（地塞米松浓度分别为0．5×10-7、1×10-6mol／L）体外培养24h。收集细胞以CD4、PD1、CXCR5流式检测Tfh的百分比，酶联免疫吸附试验（ELISA）法检测上清中抗核抗体的表达。配对t检验行2组间差异比较。结果与对照组[24h（4.3±1．2）％，72h（5．6±4．0）％]相比，体外培养24h（5．9±2．4）％及72h后（8．0±5．6）％rIL-21组Tfh细胞的百分比显著升高，差异有统计学意义（t=3．48和3．05，P=0．007和0．012）；与rIL-21组相比，培养24h（4．2±1．3）％及72h（6．2±4．4）％后rIL-21±地塞米松组Tfh细胞的百分比有所下降，但仍高于对照组，差异有统计学意义（t=4．70和2．78，P=0．001和0．019）；地塞米松显著降低T0n细胞的百分比，并具有浓度依赖性[对照组（4．0±1．2）％，低浓度地塞米松组（3．3±1．2）％，高浓度地塞米松（2．9±1．0）％，低浓度地塞米松组与对照组相比差异有统计学意义（t=3．37，P=0．003）；高浓度地塞米松组与低浓度地塞米松组相比差异有统计学意义（t=2．26，P=0．036）。各组上清中抗核抗体差异无统计学意义（P〉0．05）。结论IL-21能够增加SLE患者Tfh细胞比例，而地塞米松对Tfh细胞的产生具有抑制作用，且可对抗IL-21诱导的Tfh细胞增殖。Objective To investigate the effect of interleukin （IL）-21 and dexamethasone （Dex） treatment on the percentage of follicular helper T cells （Tfh） in patients with systemic lupus erythematosus （SLE）. Methods Peripheral blood mononuclear cells （PBMCs） obtained from 11 SLE patients were cultured in 96 well plates at 106/well with medium as the control, and with rIL-21 （200 ng/μl） or rIL-21 （200 ng/μl）± Dex （1 ×10-6 mol/L） for 24 and 72 hours as the study groups. Another： 20 samples were collected and incubated with different concentrations of Dex （0, 5×10-7 mol/L, 1×10-6 mol/L） for 24 hours. After labeling with CD4, PD1 and CXCR5 monoclonal antibodies, the proportions of Tfh ceils were assessed by flow cytometry. ELISA was used to detect supernatant antinuclear antibody （ANA） levels. Differences between groups were analyzed by paired t test. Results The percentages of Tfh cells were elevated when incubated with rlL-21 for 24 h and 72 h [24 h （4.3±1.2）%, （5.9±2.4）%; 72 h （5.6±4.0）%, （8.0±5.6）%; t=3.48 and 3.05 respectively, P=0.007 and 0.012]. Compared with those in the rlL-21 group, the percentages of Tfh cells in the rlL-21±Dex group were decreased （t=4.70 and 2.78, P=0.001 and 0.019）. Tfh cells were decreased ina dose-dependent manner when treated with Dex [24 h （4.2±1.3）%; 72 h （6.2±4.4）%; t=3.37 and 2.26, P=0.003 and 0.036]. There was no difference of supernatant ANA levels among those groups. Conclusion IL-21 can promote the proliferation of Tfh cells, while Dex inhibits Tfh cell growth and the inhibition effect is dose dependent. Tfh cells may represent a new target for the treatment of SLE.

关 键 词：红斑狼疮 系统性 地塞米松 白细胞介素21 滤泡辅助性T细胞 

分 类 号：R593.241[医药卫生—内科学]