基于生物信息学分析探究盘状红斑狼疮的关键通路、基因及免疫细胞浸润  

Analysis on key signaling pathways, genes and and immune cell infiltration in discoid lupus erythematosus based on bioinformatics

作　　者：魏姗姗 闫璐[1] 邱贤文[1] 赖宽[2] 米向斌(指导)[1] WEI Shan-Shan;YAN Lu;QIU Xian-Wen;LAI Kuan;MI Xiang-Bin(Department of Dermatology,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China)

机构地区：[1]南方医科大学珠江医院皮肤科,广州510280 [2]南方医科大学南方医院皮肤科,广州510515

出　　处：《中国免疫学杂志》2021年第5期519-523,528,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金青年项目(81803119)。

摘　　要：目的:采用生物信息学方法寻找盘状红斑狼疮(DLE)中的差异表达基因(DEGs)和免疫细胞浸润矩阵明确其功能,探讨DLE的发病机制。方法:从GEO中获取GSE81071芯片数据,以P<0.05及|logFC|>1.5为条件筛选DEGs;采用CIBERSORT反卷积法分析表达谱中22种免疫细胞浸润比例。结果:共筛选出DEGs 214个,其中上调基因178个,下调基因36个,主要富集于细胞膜外侧面、膜侧和细胞表面,通过调节dsRNA结合、趋化因子受体结合和活性参与免疫应答、固有免疫应答、防御反应等生物学过程。KEGG主要富集细胞因子-细胞因子受体相互作用、Toll样受体、病毒感染等信号通路。PPI网络分析筛选得前2个核心基因STAT1和OAS1。免疫细胞的浸润矩阵分析结果表明,活化的CD4^(+)记忆T细胞、M1巨噬细胞显著增加,而活化的树突状细胞(DCs)显著减少。结论:M1巨噬细胞和CD4^(+)记忆T细胞、DCs的活化与DLE发病机制密切相关,核心基因STAT1和OAS1可能通过细胞因子-细胞因子受体相互作用、Toll样受体等免疫相关信号通路参与DLE发生发展。Objective:To seek differentially expressed genes(DEGs) through bioinformatics methods and immune infiltration were about to identify in discoid lupus erythematosus(DLE),to clarify their functions, and to explore pathogenesis of DLE.Methods:GSE81071 dataset was downloaded from GEO database, and DEGs were screened at P<0.05 and |logFC|>1.5;CIBERSORT deconvolution method was used to analyze infiltration ratio of 22 types of immune cells in expression profile.Results:A total of 214 DEGs were screened, 178 were up-regulated and 36 were down-regulated, which were mainly enriched at outside of cell membrane, membrane side and cell surface, and involved in biological processes such as immune response, innate immune response, and defense response by regulating dsRNA binding, chemokine receptor binding and activity.KEGG was mainly enriched in cytokine-cytokine receptor interaction, Toll-like receptor and viral infection signaling pathways.2 pivot genes obtained from PPI network analysis were STAT1 and OAS1.Infiltration matrix analysis of immune cells showed that CD4^(+) memory T cells activated and macrophages M1 were significantly increased in DLE,dendritic cells(DCs) activated was significantly reduced.Conclusion:Macrophages M1 and activation of CD4^(+) memory T cells, DCs were closely associated with pathogenesis of DLE.Pivot genes STAT1 and OAS1 might participate in occurrence and development of DLE through cytokine-cytokine receptor interaction, Toll-like receptor and other immune-related signaling pathways.

关 键 词：盘状红斑狼疮 免疫细胞 生物信息学 STAT1 

分 类 号：R758.62[医药卫生—皮肤病学与性病学]