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Abstract：
To enhance the understanding of molecular mechanisms and mine previously unidentified biomarkers of pediatric atopic dermatitis, PBMC gene expression profiles were generated by RNA sequencing in infants with atopic dermatitis and age-matched controls. A total of 178 significantly differentially expressed genes (DEGs) (115 upregulations and 63 downregulations) were seen, compared with those in healthy controls. The DEGs identified included IL1β, TNF, TREM1, IL18R1, and IL18RAP. DEGs were validated by real-time RT- qPCR in a larger number of samples from PBMCs of infants with atopic dermatitis aged <12 months. Using the DAVID (Database for Annotation, Visualization and Integrated Discovery) database, functional and pathway enrichment analyses of DEGs were performed. Gene ontology enrichment analysis showed that DEGs were associated with immune responses, inflammatory responses, regulation of immune responses, and platelet activation. Pathway analysis indicated that DEGs were enriched in cytokine‒cytokine receptor interaction, immunoregulatory interactions between lymphoid and nonlymphoid cells, hematopoietic cell lineage, phosphoinositide 3-kinase‒protein kinase B signaling pathway, NK cell‒mediated cytotoxicity, and platelet activation. Furthermore, the protein‒protein interaction network was predicted using the STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database and visualized with Cytoscape software. Finally, on the basis of the protein‒protein interaction network, 18 hub genes were selected, and two significant modules were obtained. In conclusion, this study sheds light on the molecular mechanisms of pediatric atopic dermatitis and may provide diagnostic biomarkers and therapeutic targets.
摘要：
为了提高对儿童特应性皮炎分子机制的理解和挖掘以前未知的生物标志物，通过RNA测序在患有特应性皮炎的婴儿和年龄匹配的对照中产生PBMC基因表达谱。共发现178个显著差异表达基因(DEGs)(115个上调和63个下调),与健康对照组相比。确定的DEG包括IL1β，TNF,TREM1、IL18R1和IL18RAP。通过实时RT-qPCR在来自患有<12个月的特应性皮炎的婴儿的PBMC的大量样品中验证DEGs。使用DAVID（数据库注释，可视化和集成发现)数据库，进行了DEGs的功能和途径富集分析。基因本体论富集分析表明，DEGs与免疫反应有关，炎症反应，调节免疫反应，和血小板活化。通路分析表明，DEGs富含细胞因子-细胞因子受体相互作用，淋巴细胞和非淋巴细胞之间的免疫调节相互作用，造血细胞谱系，磷酸肌醇3-激酶-蛋白激酶B信号通路,NK细胞介导的细胞毒性，和血小板活化。此外，使用STRING（检索相互作用基因/蛋白质的搜索工具）数据库预测蛋白质-蛋白质相互作用网络，并使用Cytoscape软件进行可视化。最后,在蛋白质-蛋白质相互作用网络的基础上，选择了18个hub基因，并获得了两个重要的模块。总之,这项研究揭示了儿童特应性皮炎的分子机制，并可能提供诊断生物标志物和治疗靶点。
