单细胞驱动的IFN和TNF程序在抗合成酶综合征相关的间歇性肺病中协调炎症网络
Yu Fan1, Weijin Zhang2, Miaotong Su1
1Department of Pathology, Shantou University Medical College, Shantou, China.
Frontiers in immunology
|November 10, 2025
概括
单细胞在与抗合成酶综合征相关的间歇性肺病 (ASS-ILD) 中协调免疫失调. 由特定的转录因子驱动的关键干扰素和TNF信号通路,代表了ASS-ILD的潜在治疗标.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 肺部病理学 肺部病理学
背景情况:
- 与抗合成酶综合征相关的间歇性肺病 (ASS-ILD) 呈现出各种临床特征和进展.
- 驱动ASS-ILD的确切免疫病原性机制仍然不完全理解.
研究的目的:
- 在ASS-ILD.中阐明细胞类型特定的干扰素免疫特征.
- 定义涉及ASS-ILD病变发生的转录网络.
主要方法:
- 来自ASS-ILD患者和健康对照的外周血液单核细胞 (PBMC) 的单细胞RNA测序 (scRNA-seq).
- 使用AUCell,Seurat,Monocle和CellChat对大型队列 (126,026个细胞) 的综合分析.
- 转录因子活性与脱R的推断.
主要成果:
- 确定并验证了单细胞特异性干扰素刺激基因 (ISG) 活性.
- 一个特定的单细胞子集 (mono2) 显示IFNG表达升高和炎症轨迹.
- 观察到失调的II型干扰素 (IFN-II) 和瘤亡因子 (TNF) 信号,涉及单细胞,NK细胞和CD8+ T细胞.
- 关键的转录因子 (ETV5,IRF5,IRF7,RORB,RORC,SMAD1) 与炎症和纤维细胞转移途径有关.
结论:
- 单细胞是ASS-ILD中免疫失调的核心.
- 干扰素和TNF信号通路,以及已识别的转录调节器,代表了ASS-ILD的有希望的治疗点.
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