Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Front Immunol. 2023 Feb 3;14:1024041. doi: 10.3389/fimmu.2023.1024041. eCollection 2023.
Coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) are both caused by a disordered immune response and have direct and profound impacts on health care services. In this study, we implemented transcriptomic and single-cell analysis to detect common molecular and cellular intersections between COVID-19 and IBD that help understand the linkage of COVID-19 to the IBD patients.
Four RNA-sequencing datasets (GSE147507, GSE126124, GSE9686 and GSE36807) from Gene Expression Omnibus (GEO) database are extracted to detect mutual differentially expressed genes (DEGs) for IBD patients with the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to find shared pathways, candidate drugs, hub genes and regulatory networks. Two single-cell RNA sequencing (scRNA-eq) datasets (GSE150728, PRJCA003980) are used to analyze the immune characteristics of hub genes and the proportion of immune cell types, so as to find common immune responses between COVID-19 and IBD.
A total of 121 common DEGs were identified among four RNA-seq datasets, and were all involved in the functional enrichment analysis related to inflammation and immune response. Transcription factors-DEGs interactions, miRNAs-DEGs coregulatory networks, and protein-drug interactions were identified based on these datasets. Protein-protein interactions (PPIs) was built and 59 hub genes were identified. Moreover, scRNA-seq of peripheral blood monocyte cells (PBMCs) from COVID-19 patients revealed a significant increase in the proportion of CD14 monocytes, in which 38 of 59 hub genes were highly enriched. These genes, encoding inflammatory cytokines, were also highly expressed in inflammatory macrophages (IMacrophage) of intestinal tissues of IBD patients.
We conclude that COVID-19 may promote the progression of IBD through cytokine storms. The candidate drugs and DEGs-regulated networks may suggest effective therapeutic methods for both COVID-19 and IBD.
2019 年冠状病毒病（COVID-19）和炎症性肠病（IBD）都是由免疫失调引起的，它们直接且深刻地影响着医疗保健服务。在这项研究中，我们进行了转录组和单细胞分析，以检测 COVID-19 和 IBD 之间常见的分子和细胞交汇点，以帮助理解 COVID-19 与 IBD 患者的联系。
从基因表达综合数据库（GEO）中提取了四个 RNA 测序数据集（GSE147507、GSE126124、GSE9686 和 GSE36807），以检测感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的 IBD 患者的相互差异表达基因（DEGs），以寻找共同途径、候选药物、枢纽基因和调控网络。使用两个单细胞 RNA 测序（scRNA-eq）数据集（GSE150728、PRJCA003980）来分析枢纽基因的免疫特征和免疫细胞类型的比例，以发现 COVID-19 和 IBD 之间的共同免疫反应。
在四个 RNA-seq 数据集中共鉴定出 121 个共同的 DEGs，它们均参与与炎症和免疫反应相关的功能富集分析。基于这些数据集，鉴定了转录因子-DEGs 相互作用、miRNA-DEGs 核心调控网络和蛋白质-药物相互作用。构建了蛋白质-蛋白质相互作用（PPIs）网络，鉴定出 59 个枢纽基因。此外，对 COVID-19 患者外周血单核细胞（PBMCs）的 scRNA-seq 分析显示，CD14 单核细胞的比例显著增加，其中 59 个枢纽基因中的 38 个高度富集。这些基因编码炎症细胞因子，在 IBD 患者肠道组织的炎症性巨噬细胞（IMacrophage）中也高度表达。
我们的结论是，COVID-19 可能通过细胞因子风暴促进 IBD 的进展。候选药物和 DEGs 调控网络可能为 COVID-19 和 IBD 提供有效的治疗方法。
