SLC19A1 携带免疫反应性循环二核酸
Rutger D Luteijn1, Shivam A Zaver2, Benjamin G Gowen3,4
1Department of Molecular and Cell Biology, and Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, CA, USA.
Nature
|September 13, 2019
概括
研究人员确定减少的叶酸载体SLC19A1是循环二核酸 (CDN) 进入细胞的主要载体. 这一发现影响了对免疫反应,癌症免疫疗法和炎症疾病的理解.
科学领域:
- 免疫学
- 分子生物学
- 细胞生物学
背景情况:
- 细胞质DNA积累信号感染,癌症和DNA损伤,激活cGAS-STING通路.
- 通过DNA激活cGAS,合成循环单酸-氨酸单酸 (2'3'-cGAMP),这是第二个信使.
- 2' 3'- cGAMP激活STING,导致IRF3和NF- kB的激活和I型干扰素的产生.
研究的目的:
- 确定循环二核酸 (CDN) 穿越细胞膜的机制.
- 了解对目标细胞中STING通路激活至关重要的外源CDN的传输.
主要方法:
- 全基因组的CRISPR干扰屏幕用于识别CDN传送器.
- 在人体细胞中,候选输送物的消耗和过度表达.
- 评估各种细胞类型的CDN吸收和功能反应.
主要成果:
- 减少的叶酸载体SLC19A1被确定为CDN的主要载体.
- 减少SLC19A1抑制了CDN吸收和功能反应.
- 过度表达SLC19A1增强了CDN吸收和反应.
- 叶酸,硫素和甲基酸抑制了人类细胞中的CDN吸收.
结论:
- SLC19A1是负责细胞吸收CDN的主要载体.
- 这一发现对癌症免疫疗法,宿主对病原体的反应和炎症性疾病有重大影响.
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