来自微生物群的二次胆酸促进STING激活和抗瘤活性
Xinglin Yang1,2, Xing Zhang1, Weichao Li3
1Department of Immunology and Microbiology, Scripps Research.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
微生物的新陈代谢产生影响健康的胆汁酸. 这项研究发现,脱氧胆酸 (DCA) 直接激活STING,增强抗瘤免疫力,并建议新的治疗策略.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 来自微生物群的胆酸在健康和疾病中起作用.
- 它们的分子目标和机制在很大程度上仍然未知.
- 了解这些相互作用对于治疗的发展至关重要.
研究的目的:
- 为了确定微生物群衍生的二次胆酸的蛋白质标.
- 阐明脱氧醇酸 (DCA) 的作用机制.
- 研究DCA对STING信号传递和抗瘤免疫力的影响.
主要方法:
- 使用胆汁酸光亲和探测器和化学蛋白质组学.
- 研究了脱氧胆酸 (DCA) 与干扰素基因刺激器 (STING) 的结合.
- 评估了STING激活,I型干扰素信号传递,以及*ex vivo*和*in vivo*的抗瘤免疫力.
主要成果:
- 鉴定了哺乳动物细胞中二次胆酸的众多蛋白质标.
- 发现的脱氧胆酸 (DCA) 结合了STING的跨膜域.
- 已证明,DCA促进了STING的寡合化和激素刺激,增强了*ex vivo*和*in vivo*的抗瘤免疫力.
- 已显示,口服DCA产生细菌可以增强STING激动剂介导的抗瘤免疫力.
结论:
- 通过反向化学微生物学揭示了DCA对STING调节的不可预知的作用机制.
- 表明特定的二次胆酸及其相关微生物群可以影响针对STING的向疗法.
- 突出调节微生物群和胆汁酸的潜力,以增强癌症免疫治疗.
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