鉴定ACKR4作为肺动脉高血压的免疫检查点
Chen-Yu Jiang1,2, Li-Wei Wu1,2, Yi-Wei Liu1,2
1Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai Children's Medical Center (SCMC), School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Frontiers in immunology
|July 14, 2023
概括
肺动脉高血压 (PAH) 肺部降低的非典型化学因受体4 (ACKR4) 与免疫细胞的变化相关,这表明ACKR4可能在PAH进展中起到保护性免疫检查点的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 肺高血压研究 肺高血压研究
- 文字转录学 (Transcriptomics) 是一个学科.
背景情况:
- 炎症在肺动脉高血压 (PAH) 的发展中起着关键作用.
- 化基因及其受体协调免疫细胞的招募,并在PAH病变发生过程中发挥作用.
- 了解关键化学因子对于识别PAH新型治疗点至关重要.
研究的目的:
- 通过转录组分析识别参与肺动脉高血压 (PAH) 进展的关键化学因子.
- 研究非典型的化学因受体4 (ACKR4) 在PAH病变发生过程中的作用.
- 根据基因表达模式开发PAH的诊断模型.
主要方法:
- 与使用基因表达综合 (GEO) 数据库的对照组相比,对PAH患者肺部组织的基因表达差异分析.
- 基因组丰富分析 (GSEA) 用于功能和途径注释.
- 免疫细胞丰度估计的xCell算法.
- 权重基因相关网络分析 (WGCNA) 用于构建基因网络和诊断模型.
- 在低氧诱导的肺高血压 (PH) 鼠标模型中的验证.
主要成果:
- 在多个数据集中的PAH肺组织中,非典型的化学因子受体4 (ACKR4) 显著下调.
- 较低的ACKR4水平与丰富的PAH相关生物功能和途径有关.
- ACKR4表达与激活的树突细胞,Th1细胞和巨细胞的透负相关.
- 用CXCL12,COL18A1和TSHZ2基因开发了PAH的诊断模型,这些基因与ACKR4相关.
- 在肺高血压 (PH) 的动物模型中证实了ACKR4的下调.
结论:
- 人类PAH肺组织中ACKR4的下调反映了实验PH模型中的发现.
- ACKR4与免疫细胞透和功能通路的相关性表明它作为PAH的保护性免疫检查点的潜在作用.
- ACKR4代表了治疗肺动脉高血压的潜在治疗标.
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