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通过综合生物信息学分析鉴定系统性红斑狼疮CD4 T细胞中的关键基因。

Identifying key genes in CD4 T cells of systemic lupus erythematosus by integrated bioinformatics analysis.

作者信息

Li Zutong, Wang Zhilong, Sun Tian, Liu Shanshan, Ding Shuai, Sun Lingyun

机构信息

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Department of Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

出版信息

Front Genet. 2022 Aug 15;13:941221. doi: 10.3389/fgene.2022.941221. eCollection 2022.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by excessive activation of T and B lymphocytes and breakdown of immune tolerance to autoantigens. Despite several mechanisms including the genetic alterations and inflammatory responses have been reported, the overall signature genes in CD4 T cells and how they affect the pathological process of SLE remain to be elucidated. This study aimed to identify the crucial genes, potential biological processes and pathways underlying SLE pathogenesis by integrated bioinformatics. The gene expression profiles of isolated peripheral CD4 T cells from SLE patients with different disease activity and healthy controls (GSE97263) were analyzed, and 14 co-expression modules were identified using weighted gene co-expression network analysis (WGCNA). Some of these modules showed significantly positive or negative correlations with SLE disease activity, and primarily enriched in the regulation of type I interferon and immune responses. Next, combining time course sequencing (TCseq) with differentially expressed gene (DEG) analysis, crucial genes in lupus CD4 T cells were revealed, including some interferon signature genes (ISGs). Among these genes, we identified 4 upregulated genes (, and ) and 2 downregulated genes ( and ) as newfound key genes. The elevated genes showed close relationship with the SLE disease activity. In general, our study identified 6 novel biomarkers in CD4 T cells that might contribute to the diagnosis and treatment of SLE.

摘要

系统性红斑狼疮(SLE)是一种慢性自身免疫性疾病,其特征为T和B淋巴细胞过度活化以及对自身抗原的免疫耐受破坏。尽管已报道了包括基因改变和炎症反应在内的多种机制,但CD4 T细胞中的整体特征基因及其如何影响SLE的病理过程仍有待阐明。本研究旨在通过综合生物信息学确定SLE发病机制背后的关键基因、潜在生物学过程和途径。分析了来自不同疾病活动度的SLE患者和健康对照的分离外周血CD4 T细胞的基因表达谱(GSE97263),并使用加权基因共表达网络分析(WGCNA)鉴定了14个共表达模块。其中一些模块与SLE疾病活动度呈显著正相关或负相关,主要富集于I型干扰素调节和免疫反应。接下来,将时间序列测序(TCseq)与差异表达基因(DEG)分析相结合,揭示了狼疮CD4 T细胞中的关键基因,包括一些干扰素特征基因(ISGs)。在这些基因中,我们鉴定出4个上调基因(、和)和2个下调基因(和)作为新发现的关键基因。上调基因与SLE疾病活动度密切相关。总体而言,我们的研究在CD4 T细胞中鉴定出6种可能有助于SLE诊断和治疗的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7791/9420982/e5e0ae909273/fgene-13-941221-g001.jpg

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