Frank Qingyun Wang, Xiao Dang, Huidong Su, Yao Lei, Chun Hing She, Caicai Zhang, Xinxin Chen, Xingtian Yang, Jing Yang, Hong Feng, Wanling Yang
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引用次数: 0
摘要
背景:系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病:系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,转座元件(TE)被认为在其发病过程中起着重要作用。然而,对这一关系的研究还很有限。我们的研究旨在探讨TE表达与系统性红斑狼疮发病机制之间的关系:我们分析了 198 名系统性红斑狼疮患者和 84 名健康对照者的全血 RNA-seq 数据集。采用 REdiscoverTE 管道量化 TE 和其他基因的表达,识别差异表达的 TE。通过计算 TE 分数来衡量每个样本的整体 TE 表达。进行了基因本体和基因组富集分析,以探索 TE 上调的功能意义。利用独立数据集来复制结果并研究细胞类型特异性 TE 表达:我们的分析确定了两个不同的患者组:一个是高 TE 表达组,另一个是 TE 表达与对照组相当的患者组。高TE表达的患者表现出涉及核酸传感器的通路上调,TE表达与干扰素(IFN)特征密切相关。此外,这些患者还表现出细胞组成失调,包括中性粒细胞增加和调节性T细胞减少。中性粒细胞被认为是 TE 表达的主要来源,有助于 IFN 的产生:我们的研究结果表明,TE表达可能是维持干扰素通路激活的关键介质,是系统性红斑狼疮患者核酸刺激物的内源性来源。
Association of hyperactivated transposon expression with exacerbated immune activation in systemic lupus erythematosus.
Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder, and transposable elements (TEs) have been hypothesized to play a significant role in its development. However, limited research has explored this connection. Our study aimed to examine the relationship between TE expression and SLE pathogenesis.
Methods: We analyzed whole blood RNA-seq datasets from 198 SLE patients and 84 healthy controls. The REdiscoverTE pipeline was employed to quantify TE and other gene expressions, identifying differentially expressed TEs. A TE score was calculated to measure overall TE expression for each sample. Gene ontology and gene set enrichment analyses were conducted to explore the functional implications of TE upregulation. Independent datasets were utilized to replicate the results and investigate cell type-specific TE expression.
Results: Our analysis identified two distinct patient groups: one with high TE expression and another with TE expression comparable to controls. Patients with high TE expression exhibited upregulation of pathways involving nucleic acid sensors, and TE expression was strongly correlated with interferon (IFN) signatures. Furthermore, these patients displayed deregulated cell composition, including increased neutrophils and decreased regulatory T cells. Neutrophils were suggested as the primary source of TE expression, contributing to IFN production.
Conclusions: Our findings suggest that TE expression may serve as a crucial mediator in maintaining the activation of interferon pathways, acting as an endogenous source of nucleic acid stimulators in SLE patients.
期刊介绍:
Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.