IFNAR表达异常对红斑狼疮患者调节性T细胞功能的影响  

Effects of Altered IFNAR Expression on CD4^+ CD25^+ Treg Cell Dysfunction in Patients with Systemic Lupus Erythematosus

作　　者：何燕[1] 彭云[2] 谭淳予[2] 刘艺[2] 严冰[2] 

机构地区：[1]厦门大学附属第一医院风湿免疫科,厦门361000 [2]四川大学华西医院风湿免疫科,成都610041

出　　处：《四川大学学报（医学版）》2015年第2期209-213,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.30801028)资助

摘　　要：目的探讨确定Ⅰ型干扰素(IFNα)直接影响系统性红斑狼疮(SLE)患者调节性T细胞(Treg)功能的作用机制。方法流式细胞术检测20例初发活动性SLE患者和20例正常对照的外周血CD4+CD25+Treg细胞表面Ⅰ型干扰素受体(IFNAR)的表达。免疫磁珠细胞分选法(MACS)分选出外周血CD4+CD25+Treg细胞,检测外源性IFNα(500U/mL)对Treg细胞体外抑制功能的影响。流式细胞术分析外源性IFNα(500U/mL)对SLE患者Treg细胞体外凋亡、功能相关的重要分子标志(FOXP3、CTLA-4)和胞内AKT磷酸化表达水平的影响。结果与正常对照相比,SLE患者CD4+CD25+Treg细胞明显高表达IFNAR1(P=0.000 6),且与疾病活动指数评分(SLEDAI)呈正相关。外源性IFNα降低了SLE患者Treg细胞体外抑制功能。IFNα直接作用不影响SLE患者Treg细胞的凋亡和胞内FOXP3、CTLA-4的表达水平;但是明显上调Treg胞内AKT磷酸化水平。结论 SLE患者CD4+CD25+Treg细胞表面IFNAR表达异常可能是IFNα降低其免疫抑制功能的分子基础,而上调Treg胞内pAKT水平可能是其中的作用机制。Objective To explore the role of type Ⅰ interferon（IFNα）on the function of CD4^＋CD25^＋regulatory T（Treg）cells in patients with systemic lupus erythematosus（SLE）.Methods Twenty patients with newly-onset active SLE and 20 healthy controls were recruited in this study.The expressions of typeⅠinterferonαreceptor（IFNAR）on Treg cells were analyzed using flow cytometry.CD4^＋CD25^＋Treg cells were purified by magnetic-activated cell sorter（MACS）.The function of these cells was assessed in vitro with or without IFNα（500U/mL）.The effect of exogenous IFNαon the apoptosis of Treg cells and the expression level of FOXP3,CTLA-4,and pAKT in Treg cells were analyzed using flow cytometry.Results The expression levels of IFNAR1 on CD4^＋CD25^＋Treg cells were significantly higher in the SLE patients than in the healthy controls（P=0.000 6）.There was a positive correlation between the expression levels of IFNAR on Treg cells and the SLEDAI scores in the SLE patients.Exogenous IFNαimpaired the suppressive capacity of Treg cells in the SLE patients.However,neither the apoptosis of Treg cells nor the expression levels of FOXP3 and CTLA-4on Treg cells were influenced by IFNαstimulation.IFNαenhanced AKT phosphorylation in Treg cells in the SLE patients.Conclusion Altered IFNAR expression may contribute to Treg cell dysfunction in SLE patients through enhancing AKT phosphorylation in Treg cells.

关 键 词：调节性T细胞 干扰素 系统性红斑狼疮 免疫耐受 

分 类 号：R593.241[医药卫生—内科学]