[Bioinformatical analysis of function and differentiation of Th1/17 cells]

Objective To investigate the function and differentiation of 1/17 type helper T (Th1/17) cells. Methods Bioinformatics analysis was performed using a gene chip dataset (GSE104021) in GEO which contains gene expression data from Th17 cells and Th1/17 cells of healthy human subjects. Taking Th17 cells as the control, R language software was used to analyze the differentially expressed genes (DEGs) between Th17 cells and Th1/17 cells, so as to explore the main functional molecules of Th1/17 cells. After that, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) analysis of DEGs were conducted by R language software. Finally, the genes enriched into the target biological process in the GO analysis were selected for protein-protein interaction network (PPI) analysis to explore the differentiation process of Th1/17 cells. Results Analysis of DEGs showed that, compared with Th17 cells, the underexpressed genes in Th1/17 cells were interleukin 17A (IL-17A) and C-C motif chemokine receptor 4 (CCR4). The over-expressed genes were coiled-coil domain-containing 3 (CCDC3), C-C motif chemokine ligand 4 (CCL4), colony stimulating factor 2 receptor beta common subunit (CSF2RB), C-C motif chemokine ligand 5 (CCL5), interferon gamma (IFNG) and epithelial stromal interaction 1 (EPSTI1). In GO analysis, cell component analysis showed that the expression products of these DEGs were mainly located at external side of plasma membrane and the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor complex; biological process analysis showed that the expression products of DEGs were involved in the upregulation of interleukin 23 (IL-23), the chemokine-mediated signaling pathway and the upregulated chemotaxis of natural killer (NK) cells; molecular function analysis showed that the expression products of these DEGs had C-C motif chemokine 5 receptor (CCR5) binding activity, cytokine activity and interferon gamma (IFN-γ) receptor binding activity. The results of KEGG analysis showed that the DEGs were enriched in the cytokine-cytokine receptor interaction, rheumatoid arthritis, inflammatory bowel disease and chemokine signaling pathways. The GO analysis showed that DEGs IL-17A and IFNG were enriched to the biological process of upregulating IL-23 production. PPI showed that IL-17A and IFNG had biological functions of regulating cytokine production and myeloid white blood cell differentiation. Conclusion Bioinformatics analysis showed that the protein products encoded by overexpressed genes CCL4, CSF2RB, CCL5, IFNG and EPSTI1 in Th1/17 cells were potential functional effectors of Th1/17 cells. Th1/17 cells could produce IFN-γ and IL-17A, which act on macrophages and dendritic cells (DCs) derived from myeloid white blood cells, thus promoting the differentiation of macrophages and DCs and the production of IL-23. IL-23 promotes trans-differentiation of Th17 cells into Th1/17 cells.