CXCR4+ PD-L1+ 中性粒细胞在没有存活的败血症小鼠中增加
Guilherme Cesar Martelossi Cebinelli1,2, Maísa de Oliveira Leandro1,2, Antonio Edson Rocha Oliveira3
1Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School - University of Sao Paulo (USP), Sao Paulo, SP, Brazil.
表达CXCR4和PD-L1的不成熟中性粒细胞通过促进炎症和器官损伤而恶化败血症. 阻断IFN-amma可以降低这些中性粒细胞和败血症的严重程度,从而成为潜在的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 败血症病理生理学病理生理学
- 细胞免疫学 细胞免疫学
背景情况:
- 败血症涉及宿主对感染的反应失调,导致不同的临床结果.
- 中性粒细胞在败血症中观察到的高炎症表型中发挥着关键作用.
研究的目的:
- 调查中性粒细胞对败血症引起的高炎症有所贡献的免疫机制.
- 为了确定与败血症严重程度和死亡率相关的特定中性粒细胞子集.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 用于分析幸存和未幸存的CLP-败血性小鼠的免疫细胞.
- 使用流细胞计和分子分析来描述中性粒细胞种群及其功能.
主要成果:
- 没有存活的小鼠显示血液和肺部中不成熟的CXCR4+ PD-L1+中性粒细胞的频率增加.
- 发现IFN-和LPS促进中性粒细胞的PD-L1表达,与炎症和器官损伤相关.
- 废除IFN-gamma降低了对败血症的敏感性,并降低了CXCR4+ PD-L1+中性粒细胞的发生频率.
结论:
- CXCR4+ PD-L1+ 中性粒细胞与败血症和高炎症的恶化有关.
- 准CXCR4+ PD-L1+中性粒细胞群体可能为临床败血症提供治疗策略.
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