cGAS表达在与系统性硬化症相关的间歇性肺病中得到增强,并刺激炎症性肌纤维细胞激活
medRxiv : the preprint server for health sciences
|August 30, 2024
概括
循环GMP-AMP合成酶 (cGAS) 信号驱动系统性硬化症相关间歇性肺部疾病 (SSc-ILD) 的炎症和纤维化. 抑制cGAS为SSc-ILD患者提供了一个有前途的新治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 肺部病理学 肺部病理学
- 纤维化研究 纤维化研究
背景情况:
- 系统性硬化症相关的间歇性肺病 (SSc-ILD) 涉及炎症性肌纤维细胞.
- 天生的免疫传感器循环GMP-AMP合成酶 (cGAS) 在SSc-ILD病原发生中的作用目前尚不清楚.
研究的目的:
- 在SSc-ILD.中调查cGAS表达,活性和治疗潜力.
- 探索cGAS信号对SSc-ILD病原体的贡献.
主要方法:
- 在SSc-ILD组织和细胞中评估了cGAS,细胞因子和1型干扰素的表达.
- 在SSc-ILD数据集中评估cGAS激活和刺激正常人肺纤维细胞 (NHLFs).
- 在试验室中测试了cGAS抑制,在人类精确切割肺切片 (PCLS) 中,以及在白素诱导的肺纤维化小鼠模型中.
主要成果:
- cGAS,细胞因子和1型干扰素在SSc-ILD肺组织和支气管支气管洗 (BAL) 中升高.
- 该cGAS通路在SSc-ILD纤维细胞中具有构成性活性,并可通过TGFβ1或机械刺激来诱导.
- 在各种模型中,cGAS抑制降低了细胞因子,1型干扰素和αSMA的产生,包括白色素小鼠模型.
结论:
- cGAS信号传递有助于SSc-ILD中炎症性肌纤维细胞表型的发展.
- 针对cGAS或其下游途径为SSc-ILD提供了一个新的治疗途径.
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