端粒酶逆转录酶在通过调节cGAS-STING通路来编程微环境中的作用在进化过程中得到了保留
Semih Can Akincilar1, Kerem Fidan1, Naveen Kumar1
1Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Nature cell biology
|August 7, 2025
概括
端粒酶成分TERT通过cGAS-STING通路直接调节炎症,独立于其端粒维护作用. 免疫细胞中这种保存的功能为炎症性疾病提供了新的治疗点.
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:
- 端粒酶全酶以端粒维护和调节来自端粒DNA损伤的炎症而闻名.
- 端粒酶直接控制炎症的精确分子机制尚未完全理解.
研究的目的:
- 研究端粒酶逆转录酶 (TERT) 在调节炎症中的非端粒酶直接作用.
- 阐明涉及TERT介导炎症调节的特定途径和细胞类型.
主要方法:
- 利用小鼠和斑马鱼的肠道炎症模型.
- 分析了来自大肠炎和克罗恩病患者的人体样本.
- 采用了一种具有非活性逆转录酶的TERT鼠标模型 (TERTVAA).
- 应用分子,药理和单细胞分析.
主要成果:
- TERT通过细胞质cGAS-STING核酸感应通路直接调节炎症,以细胞类型特定的方式.
- 这种TERT功能在各个物种和人类炎症性疾病中在进化过程中得到了保留.
- 鉴定了一种髓状子群 (T-MACs),其中TERT增强STING激活并启动1型干扰素反应,独立于其酶活性或端粒长度.
结论:
- TERT通过调节cGAS-STING通路,在调节炎症方面发挥着直接的,非正规的作用.
- 这一发现揭示了TERT.通过免疫调节的新机制.
- 建议TERT作为癌症治疗之外的炎症状况的潜在治疗标.
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