衰老细胞衍生的细胞外囊对先天性免疫细胞功能的影响
Yung-Yi Chen1, Jack Sullivan1,2, Shaun Hanley1
1Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.
Advanced biology
|October 23, 2024
概括
衰老的细胞外囊泡 (SEVs) 被免疫细胞吸收,促进单细胞中的炎症反应. 这表明SEVs有助于随着衰老观察到的炎症加剧.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
背景情况:
- 细胞外囊泡 (EVs) 是细胞间通信的关键媒介,携带着影响细胞功能的分子载荷.
- 与衰老相关的分泌表型 (SASP) 涉及释放EVs (SEVs),可以调节瘤微环境和全身炎症.
- 了解SEVs的免疫调节作用对于破译与年龄相关的炎症过程至关重要.
研究的目的:
- 研究来自老化 (SEV) 和非老化 (N-SEV) 纤维细胞的EV与免疫细胞之间的相互作用.
- 确定SEVs对单细胞激活和炎症性细胞因子产生的影响.
- 分析SEV和N-SEV之间货物的分子差异及其对基因表达的影响.
主要方法:
- 用单细胞,中性粒细胞和暴露于SEVs和N-SEVs的B细胞进行细胞分析.
- 脂聚糖 (LPS) 诱导的瘤缩因子-α (TNF-α) 在单细胞THP-1细胞系中的生产试验.
- 用SEVs或N-SEVs治疗的THP-1细胞的RNA测序和蛋白质组分析.
主要成果:
- SEVs是由单细胞,中性粒细胞和B细胞通过内细胞分裂而细胞化.
- 在SEV前期治疗显著增加THP-1细胞中LPS诱导的TNF-α的产生 (32-66%的增加).
- 通过N-SEV治疗,THP-1细胞减少了TNF-α的分泌 (20%的减少).
- 在SEV和N-SEV之间观察到不同的基因表达特征和货物组成,SEV丰富了SLITS/ROBO信号和代谢通路.
结论:
- SEVs被细胞和B细胞识别和内化.
- 在刺激后,SEVs在单细胞中促进一种亲炎性表型.
- 这些发现突出了一个潜在的机制,即SEVs有助于与年龄有关的炎症.
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