Abstract
BackgroundType 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by severe loss of pancreatic β cells. Immune cells are key mediators of β cell destruction. This study attempted to investigate the role of immune cells and immune-related genes in the occurrence and development of T1DM.MethodsThe raw gene expression profile of the samples from 12 T1DM patients and 10 normal controls was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by Limma package in R. The least absolute shrinkage and selection operator (LASSO)—support vector machines (SVM) were used to screen the hub genes. CIBERSORT algorithm was used to identify the different immune cells in distribution between T1DM and normal samples. Correlation of the hub genes and immune cells was analyzed by Spearman, and gene-GO-BP and gene-pathway interaction networks were constructed by Cytoscape plug-in ClueGO. Receiver operating characteristic (ROC) curves were used to assess diagnostic value of genes in T1DM.ResultsThe 50 immune-related DEGs were obtained between the T1DM and normal samples. Then, the 50 immune-related DEGs were further screened to obtain the 5 hub genes. CIBERSORT analysis revealed that the distribution of plasma cells, resting mast cells, resting NK cells and neutrophils had significant difference between T1DM and normal samples. Natural cytotoxicity triggering receptor 3 (NCR3) was significantly related to the activated NK cells, M0 macrophages, monocytes, resting NK cells, and resting memory CD4+ T cells. Moreover, tumor necrosis factor (TNF) was significantly associated with naive B cell and naive CD4+ T cell. NCR3 [Area under curve (AUC) = 0.918] possessed a higher accuracy than TNF (AUC = 0.763) in diagnosis of T1DM.ConclusionsThe immune-related genes (NCR3 and TNF) and immune cells (NK cells) may play a vital regulatory role in the occurrence and development of T1DM, which possibly provide new ideas and potential targets for the immunotherapy of diabetes mellitus (DM).
Highlights
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by severe loss of pancreatic β cells
The raw identification and functional enrichment analysis of the immune‐related Differentially expressed genes (DEG) The 1639 immune-related genes were overlapped with the DEGs using the Venn diagram, getting 50 immunerelated DEGs (Fig. 2a) that were used for subsequent analysis
The analysis of KEGG pathway indicated that these genes were mainly enriched in Type 1 diabetes mellitus pathway (Fig. 2c and Additional file 4: Table S4), further verifying that the immune-related DEGs played a vital role in the occurrence and development of T1DM
Summary
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by severe loss of pancreatic β cells. Type 1 diabetes mellitus (T1DM) caused by autoimmune reaction is a major subtype of diabetes, and is mostly prevalent in adolescents and childhood [1]. Over the past 30 years, insulin therapy, immunotherapy and some potential therapies such as cell therapy are the main treatments for diabetes. These treatments usually have some problems, for instance, insulin therapy can cause a series of complications, while immunotherapy may impact acquired immunity and the efficacy is short-term [4,5,6]
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