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. 2021 Jan;10(1):204-214.
doi: 10.21037/tau-20-943.

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

Tianying Yang  1   2 , Jiawei Li  1   2 , Yichen Jia  1   2 , Chunchen Yang  3 , Ruirui Sang  3 , Tongyu Zhu  1   2 , Ming Xu  1   2 , Ruiming Rong  1   2   3 , Cheng Yang  1   2   4
Affiliations

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

Tianying Yang et al. Transl Androl Urol. 2021 Jan.

Abstract

Background: In the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.

Methods: Microarray data of rat gene expression profiles under accession number GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.

Results: Three hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.

Conclusions: These key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.

Keywords: Transplant tolerance; bioinformatics analysis; differentially expressed genes (DEGs); gene ontology (GO); protein-protein network.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-943). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The general design of the analysis. (A) Flowchart and major procedures for the bioinformatics analysis of GSE28545; (B) the value distribution of each sample. The blue values are from the tolerant samples (GSM706861–GSM706863) and the red values are from syngenic samples (GSM706864 and GSM706865); cross-comparisons can be performed when these values are at the same level. DAVID, Database for Annotation, Visualization and Integrated Discovery; PPI, protein-protein interaction; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 2
Figure 2
Heatmap of the differentially expressed genes (DEGs). The left three columns represent the tolerant samples and the two right columns show the syngenic samples. Each row represents one single DEG. Red and green colors represent high and low expression, respectively. The brighter color indicates greater variation.
Figure 3
Figure 3
The top five Gene Ontology (GO) functions for the DEGs, including biological process (A), cellular component (B), molecular function (C) and KEGG pathway (D). The horizontal ordinate is −log10 (P value), so the smaller P values are larger along the abscissa. DEGs, differentially expressed genes; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 4
Figure 4
The protein-protein interaction (PPI) network, showing the string interactions between the DEGs. The upregulated genes are colored red while the downregulated genes are blue. DEGs, differentially expressed genes
Figure 5
Figure 5
The hub genes in the protein-protein interaction (PPI) network. The top 15 hub genes ranked by degree of connectivity are shown as a cluster.
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