B-1a细胞清理NET,以减轻败血症的发生
Kensuke Murata1, Atsushi Murao1, Chuyi Tan1
1Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY 11030, United States.
Journal of leukocyte biology
|March 14, 2024
概括
在败血症期间,B-1a细胞减少有害的中性粒细胞外细胞陷 (NETs). 这些调节性B细胞通过直接接触和IgM介导的细胞分解清除NET,改善了败血症小鼠的生存率.
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
- 细胞生物学 细胞生物学
背景情况:
- 中性细胞细胞外陷 (NETs) 对于病原体防御至关重要,但当过度生产时会导致败血症引起的炎症和组织损伤.
- 细胞外冷诱导性RNA结合蛋白 (eCIRP) 是一种与损伤相关的分子模式,在败血症期间促进NET形成.
- B-1a细胞是产生天然IgM和IL-10的调节性B淋巴细胞,在减轻败血症方面可能发挥作用.
研究的目的:
- 研究B-1a细胞在清除NET和预防败血症引起的损伤中的作用.
- 阐明B-1a细胞调节NET形成和细胞形成的机制.
主要方法:
- 在小鼠中使用腹腔内注射大肠杆菌诱导败血症.
- 腹膜B-1a细胞计数通过流细胞计量进行评估.
- 在败血症小鼠中,B-1a细胞通过腹膜内补充;在与B-1a细胞共同培养的中性粒细胞 (接触与非接触) 中分析了NET形成,并使用eCIRP刺激.
主要成果:
- 败血症小鼠显示腹腔内B-1a细胞的显著减少.
- 补充B-1a细胞减少了NET,炎症和损伤标志物,并增加了败血症小鼠的生存率.
- B-1a细胞以接触依赖的方式抑制了eCIRP诱导的NET形成,并通过天然IgM促进了NET细胞形成.
结论:
- B-1a细胞通过减少NET负担在败血症中发挥保护作用.
- 细胞间直接接触和自然的IgM介导的细胞分裂是B-1a细胞介导的NET清除的关键机制.
- B-1a细胞内化和溶解NET,减轻败血症引起的病理.
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