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与年龄相关的自我DNA积累可能会加速老鼠和人类类风湿性关节炎的关节炎
Wei-Dan Luo1,2,3, Yu-Ping Wang1,3,4, Jun Lv4
1Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macau, China.
Nature communications
|July 20, 2023
概括
衰老会增加DNA碎片,通过免疫激活促进类风湿性关节炎 (RA). TREX1酶调节了这一过程,为RA治疗提供了潜在的点.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 分子生物学分子生物学
背景情况:
- 风湿性关节炎 (RA) 的发病率随着年龄的增长而上升.
- 在自身免疫性疾病中观察到DNA碎片的积累.
- 衰老,DNA碎片和RA病原体之间的联系尚未得到充分理解.
研究的目的:
- 调查DNA片段和TREX1外核酶在类风湿性关节炎发病过程中的作用.
- 探索RA中衰老,DNA碎片和免疫系统激活之间的机制关系.
主要方法:
- 使用辅助剂诱导的关节炎 (AIA) 鼠标模型.
- 操纵的TREX1水平 (过度表达和条件删除).
- 评估了循环中的自由 (cf) DNA和免疫激活标记物的水平.
- 研究了AP-1转录因子 (c-Jun和c-Fos) 的作用.
主要成果:
- 随着年龄的增长,DNA碎片的积累促进了AIA大鼠的异常免疫激活.
- 过度表达TREX1抑制了结膜炎症.
- 删除TREX1导致cfDNA增加,免疫激活增加,并加剧了AIA症状.
- AP-1失调与TREX1表达和SASP诱导有关.
结论:
- 在RA病变发生过程中,DNA片段充当炎症媒介.
- 由AP-1调节的TREX1在控制细胞免疫力方面起着至关重要的作用.
- TREX1是治疗RA和其他自身免疫性疾病的潜在治疗标.
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