鼻黏膜组织CD4^(+)T细胞参与季节性变应性鼻炎发病机制的生物信息学分析  

Role of CD4^(+)T cells from nasal mucosa in the pathogenesis of patients with seasonal allergic rhinitis

作　　者：侯凌霄[1] 展长翠 许安廷[1] 范新泰 王娜[1] HOU Lingxiao;ZHANG Changcui;XU Anting;FAN Xintai;WANG Na(Department of Otorhinolaryngology&Head and Neck Surgery,The Second Hospital of Shandong University,Jinan 250033,Shandong,China;Department of Otorhinolaryngology&Head and Neck Surgery,Dongping People's Hospital,Taian 271506,Shandong,China)

机构地区：[1]山东大学第二医院耳鼻喉头颈外科,山东济南250033 [2]东平县人民医院耳鼻喉头颈外科,山东泰安271506

出　　处：《山东大学耳鼻喉眼学报》2023年第4期96-104,共9页Journal of Otolaryngology and Ophthalmology of Shandong University

摘　　要：目的探讨CD4^(+)T细胞参与季节性变应性鼻炎(seasonal allergic rhinitis,SAR)发生发展的关键生物学机制。方法获取基因表达数据库(gene expression omnibus,GEO)中GSE49782数据集的基因表达数据,使用GEO2R在线筛选该数据集中SAR患者基线水平及桦树花粉提取物激发后的鼻腔黏膜活检组织所分离提取的CD4^(+)T细胞之间的差异表达基因(differentially expressed genes,DEGs)。使用Metascape进行基因本体论(gene ontology,GO)及京都基因百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。通过STRING数据库分析DEGs所编码蛋白的相互作用,使用X2K查找DEGs与其相应转录因子之间的调控关系。结果以adj.P<0.05且|logFC|>0.585为标准共筛选出74个DEGs,其中包括8个上调基因和66个下调基因。GO和KEGG富集分析显示DEGs显著富集于细胞间连接、肌动蛋白丝束组装等相关的蛋白和通路。通过DEGs的蛋白-蛋白相互作用网络和转录因子分析进行进一步分析,筛选出5个核心DEGs(ASL、CTTN、EPS8、FNBP1L及SH3KBP1)及SIN3A、CDK1和GSK3B等关键转录因子和重要激酶。结论鼻黏膜组织中的CD4^(+)T细胞可能通过ASL、CTTN、EPS8、FNBP1L及SH3KBP1核心DEGs及SIN3A、CDK1和GSK3B等关键转录因子和重要激酶调节细胞间连接等一系列生物学过程影响SAR的发生发展,为进一步深入理解SAR发生发展的分子生物学机制,探索其治疗的有效方案提供了新的见解及思路。Objective To explore the key biological mechanisms of CD4^(+)T cells involved in the pathogenesis of seasonal allergic rhinitis(SAR).Methods Gene expression data were obtained from the GSE49782 dataset in the Gene Expression Omnibus.GEO2R was used to screen the genes differentially expressed between CD4^(+)T cells isolated and extracted from nasal mucosa biopsy tissues of SAR patients before and after stimulation by a birch pollen extract.Metascape was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The STRING dataset was used to analyze the proteinprotein interactions of differentially expressed genes(DEGs).X2K was used to explore the regulatory relationship between DEGs and their transcription factors.Results A total of 74 DEGs were screened based on an adjusted Pvalue of<0.05 and|logFC|>0.585.Of these DEGs,8 were upregulated and 66 were downregulated.GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in proteins and pathways related to the intercellular junction and actin filament assembly.Through transcription factor analysis of DEGs and further analysis of the protein-protein interaction networks,five hubs of DEGs(ASL,CTTN,EPS8,FNBP1L,and SH3KBP1)as well as key transcription factors and important kinases(SIN3A,CDK1,and GSK3B)were found to play important roles in the pathogenesis of SAR.Conclusion CD4^(+)T cells in the nasal mucosa may affect the pathogenesis of SAR through a series of biological processes,for example,by regulating intercellular connections through their key expressed genes.The ASL,CTTN,EPS8,FNBP1L,and SH3KBP1 hubs of DEGs as well as key transcription factors and important kinases,such as SIN3A,CDK1,and GSK3B,could be involved in the occurrence and development of SAR.These novel findings will further our understanding of the molecular biological mechanism of SAR occurrence and development and will help in exploring effective therapeutic options.

关 键 词：季节性变应性鼻炎 CD4^(+)T细胞 差异表达基因 生物信息学分析 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]