Department of Resipiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Department of Rheumatism and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.
Sci Rep. 2024 May 27;14(1):12042. doi: 10.1038/s41598-024-62758-w.
T cells are one of the main cell types shaping the immune microenvironment in chronic obstructive pulmonary disease (COPD). They persist andplay cytotoxic roles. The purpose of this study aimed to explore the potential related-genes of T cells in lung tissue of COPD. Chip data GSE38974 and single_celldata GSE196638 were downloaded from the GEO database. Difference analyses and WGCNA of GSE38974 were performed to identify DEGs and the modules most associated with the COPD phenotype. Various cell subsets were obtained by GSE196638, and DEGs of T cells were further identified. GO, GSEA and KEGG enrichment analyses were conducted to explore the biological functions and regulatory signaling pathways of the DEGs and DEGs of T cells. The intersection of the DEGs, module genes and DEGs of T cells was assessed to acquire related-genes of T cells. The mRNA and protein expression levels of related-genes ofT cells were verified in lung tissue of mouse with emphysema model. Based on GSE38974 difference analysis, 3811 DEGs were obtained. The results of WGCNA showed that the red module had the highest correlation coefficient with the COPD phenotype. GSE196638 analysis identified 124 DEGs of T cells. The GO, GSEAand KEGG enrichment analyses mainly identified genes involved in I-kappaB kinase/NF-kappaB signaling, receptor signaling pathway via STAT, regulationof CD4-positive cells, regulation of T-helper cell differentiation, chemokine signaling pathway, Toll-likereceptor signaling pathway, CD8-positive cells, alpha-beta T cell differentiation, MAPK signaling pathway and Th17 cell differentiation. The DEGs, genes of the red module and DEGs of T cells were overlapped to acquire FOXO1 and DDX17. The results of RT-qPCR and Western Blot indicate that the mRNA and protein expression levels of FOXO1 and DDX17 in lung tissue of emphysema mice were significantly higher compared with those in air-exposed mice. FOXO1 as well as DDX17 may be related-genesof T cells in lung tissue of patient with COPD, and their participation in the biological processes of different signaling pathways may inspire further COPD research.
T 细胞是塑造慢性阻塞性肺疾病（COPD）免疫微环境的主要细胞类型之一。它们持续存在并发挥细胞毒性作用。本研究旨在探索 COPD 患者肺组织中 T 细胞的潜在相关基因。从 GEO 数据库中下载芯片数据 GSE38974 和单细胞数据 GSE196638。对 GSE38974 进行差异分析和 WGCNA，以鉴定与 COPD 表型最相关的 DEGs 和模块。通过 GSE196638 获取各种细胞亚群，并进一步鉴定 T 细胞的 DEGs。进行 GO、GSEA 和 KEGG 富集分析，以探讨 DEGs 和 T 细胞 DEGs 的生物学功能和调控信号通路。评估 DEGs、模块基因和 T 细胞 DEGs 的交集，以获得 T 细胞的相关基因。在肺气肿模型小鼠的肺组织中验证 T 细胞相关基因的 mRNA 和蛋白表达水平。基于 GSE38974 差异分析，获得 3811 个 DEGs。WGCNA 的结果表明，红色模块与 COPD 表型的相关性最高。GSE196638 分析鉴定出 124 个 T 细胞 DEGs。GO、GSEA 和 KEGG 富集分析主要鉴定出参与 I-kappaB 激酶/NF-kappaB 信号、STAT 受体信号通路、CD4+细胞调节、T 辅助细胞分化调节、趋化因子信号通路、Toll 样受体信号通路、CD8+细胞、α-β T 细胞分化、MAPK 信号通路和 Th17 细胞分化的基因。DEGs、红色模块基因和 T 细胞 DEGs 重叠获得 FOXO1 和 DDX17。RT-qPCR 和 Western Blot 的结果表明，肺气肿小鼠肺组织中 FOXO1 和 DDX17 的 mRNA 和蛋白表达水平明显高于空气暴露小鼠。FOXO1 和 DDX17 可能是 COPD 患者肺组织中 T 细胞的相关基因，它们参与不同信号通路的生物学过程可能为进一步的 COPD 研究提供启示。
