Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time-series data
Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time-series data
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DOI：
10.3892/mmr.2017.8366
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发表时间：
2018-03-01
影响因子：
3.4
通讯作者：
Xu, Shuxiong
中科院分区：
文献类型：
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作者：
Bai, Xiaofeng;Shi, Hua;Xu, Shuxiong
人叉头盒P3（FOXP 3）（+）分化簇（CD）25（+）CD 4（+）调节性T细胞（TCR 4）是一种表达CD 4、CD 25和FOXP 3的T细胞，它们对维持免疫稳态至关重要。本研究旨在确定Treg功能的机制。GSE 11292数据集从Gene Expression Omnibus下载，其包括来自Treg细胞在19个时间点（0-360 min）（等间隔20 min）的数据，以及相应的重复样品。然而，在时间点120分钟的Treg细胞的数据缺失。利用Mfuzz软件包，通过聚类分析确定关键基因。随后，使用Cytoscape软件构建调控网络和蛋白质-蛋白质相互作用（PPI）网络，并将其合并为集成网络。使用Database for Annotation、Visualization和Integrated Discover软件，对参与PPI网络的基因进行富集分析。聚类分析得到聚类1（包括292个基因）、聚类2（包括111个基因）、聚类3（包括194个基因）和聚类4（包括103个基因）。在PPI网络中，簇1中的GAPDH（度，40）、簇3中的Janus激酶2（JAK 2）（度，10）和信号转导和转录激活因子5A（STAT 5A）（度，9）以及簇4中的肿瘤坏死因子（TNF）（度，26）和白细胞介素2（IL 2）（度，22）具有较高的度。此外，有研究表明，几种基因可能通过靶向其他基因[例如microRNA（miR）-146 b-3pTNF、miR-146 b-5 pTNF、miR-142- 5 pTNF和含有28（TRIM 28）GAPDH的三联基序]而在Treg功能中发挥作用。富集分析表明IL 2和TNF在免疫应答和T细胞受体信号通路中富集。总之，TRIM 28靶向的GAPDH、miR-146 b-3 p、miR-146 b-5 p和miR-142- 5 p靶向的TNF以及JAK 2、IL 2和STAT 5A可能在Treg功能中发挥重要作用。
Human forkhead box P3 (FOXP3)(+) cluster of differentiation (CD)25(+)CD4(+) regulatory T cells (Tregs) are a type of T cell that express CD4, CD25 and FOXP3, which are critical for maintaining immune homeostasis. The present study aimed to determine the mechanisms underlying Treg function. The GSE11292 dataset was downloaded from the Gene Expression Omnibus, which included data from Treg cells at 19 time points (0-360 min) with an equal interval of 20 min, and corresponding repeated samples. However, data for Treg cells at time point 120 min were missing. Using the Mfuzz package, the key genes were identified by clustering analysis. Subsequently, regulatory networks and protein-protein interaction (PPI) networks were constructed and merged into integrated networks using Cytoscape software. Using Database for Annotation, Visualization and Integrated Discover software, enrichment analyses were performed for the genes involved in the PPI networks. Cluster 1 (including 292 genes), cluster 2 (including 111 genes), cluster 3 (including 194 genes) and cluster 4 (including 103 genes) were obtained from the clustering analysis. GAPDH (degree, 40) in cluster 1, Janus kinase 2 (JAK2) (degree, 10) and signal transducer and activator of transcription 5A (STAT5A) (degree, 9) in cluster 3, and tumor necrosis factor (TNF) (degree, 26) and interleukin 2 (IL2) (degree, 22) in cluster 4 had higher degrees in the PPI networks. In addition, it was indicated that several genes may have a role in Treg function by targeting other genes [e.g. microRNA (miR)-146b-3pTNF, miR-146b-5pTNF, miR-142-5pTNF and tripartite motif containing 28 (TRIM28)GAPDH]. Enrichment analyses indicated that IL2 and TNF were enriched in the immune response and T cell receptor signaling pathway. In conclusion, GAPDH targeted by TRIM28, TNF targeted by miR-146b-3p, miR-146b-5p and miR-142-5p, in addition to JAK2, IL2, and STAT5A may serve important roles in Treg function.