Open Access

Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data

  • Authors:
    • Xiaofeng Bai
    • Hua Shi
    • Mingxi Yang
    • Yuanlin Wang
    • Zhaolin Sun
    • Shuxiong Xu
  • View Affiliations

  • Published online on: December 29, 2017     https://doi.org/10.3892/mmr.2017.8366
  • Pages: 3647-3657
  • Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑3p→TNF, miR‑146b‑5p→TNF, miR‑142‑5p→TNF 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.
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March-2018
Volume 17 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Bai X, Shi H, Yang M, Wang Y, Sun Z and Xu S: Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data. Mol Med Rep 17: 3647-3657, 2018
APA
Bai, X., Shi, H., Yang, M., Wang, Y., Sun, Z., & Xu, S. (2018). Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data. Molecular Medicine Reports, 17, 3647-3657. https://doi.org/10.3892/mmr.2017.8366
MLA
Bai, X., Shi, H., Yang, M., Wang, Y., Sun, Z., Xu, S."Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data". Molecular Medicine Reports 17.3 (2018): 3647-3657.
Chicago
Bai, X., Shi, H., Yang, M., Wang, Y., Sun, Z., Xu, S."Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data". Molecular Medicine Reports 17, no. 3 (2018): 3647-3657. https://doi.org/10.3892/mmr.2017.8366