m6A修饰相关基因IFIT5与系统性红斑狼疮疾病的关联研究  

Associations between m6A related-mRNA IFIT5 and systemic lupus erythematosus

作　　者：吴俊 李尚洁 张杰[2] 叶冬青 倪进东 WU Jun;LI Shangjie;ZHANG Jie;YE Dongqing;NI Jindong(Department of Epidemiology and Biostatistics,School of Public Health,Guangdong Medical University,Dongguan 523808,China;School of Public Health,Anhui University of Science and Technology,Hefei 231131,China)

机构地区：[1]广东医科大学公共卫生学院流行病与卫生统计学系,东莞523808 [2]安徽理工大学公共卫生学院,合肥231131

出　　处：《中华疾病控制杂志》2023年第12期1455-1460,共6页Chinese Journal of Disease Control & Prevention

基　　金：广东省基础与应用基础研究基金区域联合基金(2022A1515111042);国家自然科学基金(81872693,81872687)。

摘　　要：目的N6-甲基腺嘌呤(N6-methyladenosine,m6A)修饰通过调节mRNA表达及功能参与免疫炎症过程逐渐被报道,但在系统性红斑狼疮(systemic lupus erythematosus,SLE)中研究有限。故本研究将初步探索m6A修饰相关mRNA表达与SLE的关联及影响。方法利用实时定量聚合酶链反应和蛋白质印迹实验验证m6A修饰相关干扰素诱导蛋白5(interferon induced protein with tetratricopeptide repeats 5,IFIT5)在SLE患者T淋巴细胞(T细胞)中表达情况;进一步分析IFIT5差异表达与患者临床表现和临床用药之间的关系。构建干扰和过表达IFIT5的Jurkat细胞系,流式细胞术分析T细胞表型及相关细胞因子表达情况。结果与正常对照相比,SLE中高表达的IFIT5上m6A修饰显著增强;患者T细胞中IFIT5基因表达和蛋白水平均上调(均P<0.05),且与SLE患者疾病活动程度有关(rs=0.388,P=0.028)。Jurkat细胞实验发现,敲低IFIT5显著抑制细胞增殖和加速细胞凋亡,并触发肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)分泌且降低白介素-2(interleukin-2,IL-2)和白介素-6(interleukin-6,IL-6)的表达。结论SLE疾病中IFIT5高表达与m6A修饰相关;m6A修饰相关的IFIT5在SLE患者T细胞中高表达,且参与T细胞增殖和凋亡及炎症因子表达。故m6A修饰相关IFIT5可能参与SLE患者T细胞免疫炎症反应,但确切机制值得进一步研究。Objective N6-methyladenosine(m6A)methylation involved in immuno-inflammatory responses via the regulation of mRNA expression and function is reported,but its limit is in systemic lupus erythematosus(SLE).Therefore,this study will initially explore the associations of m6A-related mRNA expression with SLE.Methods Real-time quantitative polymerase chain reaction and western blot were used to validate the expression levels of m6A-related IFIT5in T cells of patients with SLE.Following that,the correlations between IFIT5and clinical characteristics,laboratory parameters and treatment of patients with SLE were analyzed.Further functional experiments were conducted to establish the Jurkat cell lines with silencing IFIT5 for exploration of the alteration of T cells and immune inflammatory cytokines(TNF-α,IL-2,and IL-6).Results Compared with normal controls,m6A modification of highly expressed IFIT5 in SLE patients was significantly enhanced.The expression levels of IFIT5 were steadily up-regulated in the T cells of patients with SLE,and were closely associated with the degree of disease activity in patients with SLE.Cell experiments showed that silencing IFIT5 significantly inhibited T cell proliferation and accelerated apoptosis,as well as triggered tumor necrosis factor-alpha(TNF-α)secretion and induced the expression levels of interleukin-2(IL-2)and interleukin-6(IL-6).Conclusion The high expression level of IFIT5 is related to m6A modification,it is also up-regulated in the T cells of patients with SLE,which participate in the immune inflammatory responses of Jurkat cells,and the specific mechanism deserves further study.

关 键 词：系统性红斑狼疮 N6-甲基腺嘌呤 干扰素诱导蛋白5 

分 类 号：R181[医药卫生—流行病学]