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早期和严重类风湿性关节炎中中性粒细胞转录组的复杂性:微RNAs的作用?
Michele Fresneda Alarcon1, Genna Ali Abdullah1, John Alexander Beggs2
1Institute of Life Course and Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, United Kingdom.
Journal of leukocyte biology
|July 1, 2025
概括
严重类风湿性关节炎中性粒细胞表现出改变的基因表达,包括干扰素通路激活和增加的microRNA-96-5p和microRNA-183-5p. 这表明,在这种情况下,微RNA驱动的机制调节了中性粒细胞的激活.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 中性粒细胞是关键的先天性免疫细胞,与类风湿性关节炎 (RA) 病原发生有关.
- 中性粒细胞激活对于RA进展至关重要,受基因表达动态的影响.
研究的目的:
- 为了研究中性粒细胞转录组在严重的,甲状腺抗性RA.
- 为了确定基因表达特征和调节机制驱动中性粒细胞激活在RA.
主要方法:
- RNA测序 (RNAseq) 来分析RA患者和健康对照中的中性粒细胞转录组.
- 基因组变异分析,以探索转录组异质性.
- 与已发表的单细胞RNAseq数据集进行比较.
主要成果:
- 确定了RA中性粒细胞的独特基因表达特征,其特征是I型干扰素特征和与脱粒化,NETosis和氧化应激相关的基因.
- 在RA中性粒细胞中检测到升高的miR-96-5p和miR-183-5p,这意味着它们与干扰素通路调节有关.
- 在RA血清中观察到中性粒细胞外细胞陷 (NET) 碎片的增加,并确定了具有明显中性粒细胞激活配置文件的患者子组.
结论:
- 在RA中中性粒细胞转录组表现出显著的异质性,不同的子集显示了增强的脱粒化,细胞毒性,炎症或干扰素激活的概况.
- 包括miR-146a-5p,miR-155-5p,miR-183-5p和miR-96-5p在内的微RNA被认为是RA中活性中性粒细胞表型的关键调节者.
- 这些发现突出了微RNA驱动的机制,用于控制类风湿性关节炎中中性粒细胞的行为.
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