干扰素反应特征与系统性红斑狼患者中性粒细胞中可转移元素的表达增加有关
bioRxiv : the preprint server for biology
|June 12, 2025
概括
系统性红斑狼 (SLE) 中性粒细胞表现出可转移元素 (TE) 表达的增加,特别是在具有I型干扰素 (IFN) 签名的患者中. 这种增加的TE活性与疾病严重程度和改变的基因剪接相关.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 系统性红斑狼 (SLE) 是一种自身免疫性疾病,其特点是慢性炎症和自身抗体的产生,其潜在机制尚不清楚.
- 中性粒细胞与SLE的发病有关,患者中常见的是I型干扰素 (IFN) 签名.
- 之前的研究表明,SLE外周血液细胞中可移植元素 (TE) 转录的增加.
研究的目的:
- 调查SLE患者中性粒细胞中不同TE类的表达水平.
- 探索IFN刺激基因 (ISG) 表达增加,TE表达和SLE疾病严重程度之间的关系.
主要方法:
- 分析SLE患者中性粒细胞 (n=23) 和健康对照组 (n=10) 的已发表的RNA测序数据.
- 在基因表达的基础上,将SLE患者分为IFN阳性 (IFNpos) 和IFN阴性 (IFNneg) 组.
- 使用的管道用于TE检测和分析ISG签名和TE家族表达.
主要成果:
- 与健康对照组和IFN阴性SLE患者相比,IFNpos SLE患者表现出ISG和多个TE家族的显著增加.
- 映射TEs的表达增加与近邻的上调基因相关,主要是在ISG的内基因内 (~80%的上调TEs).
- 特定的TE家族与SLE疾病活性有很强的相关性,ISG内核中的高TE表达与部分内核保留和拼接变化有关.
结论:
- 中性粒细胞中TE表达的增加是IFNpos SLE患者的特征,这表明IFN反应和TE去抑制之间存在机械联系.
- 在ISG内部存在高表达的TE,与拼接变化相关,这是一种需要进一步调查的新发现.
- 中性粒细胞中TE表达模式为SLE病原和疾病活性提供了潜在的见解.
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