NET形成是一个默认的表观遗传程序,由apoptotic中性粒细胞中PAD4控制
Yanfang Peipei Zhu1,2, Mary Speir3,4, ZheHao Tan1
1Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
Science advances
|December 20, 2023
概括
中性细胞细胞外陷 (NETs) 参与病原体防御和疾病. 这项研究表明,气体皮质素E (GSDME) 在中性粒细胞亡过程中调解基因素素化,这是NET形成的关键步骤.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 中性细胞外细胞陷 (NETs) 在免疫和疾病中起着双重作用.
- NETosis,以素基因素特征,此前被认为是独立于亡.
- 达尔基宁减小酶4 (PAD4) 产生素基因组.
研究的目的:
- 为了研究亡和NETosis之间的关系.
- 为了阐明气体皮质E (GSDME) 在中性粒细胞亡期间在NET形成中的作用.
主要方法:
- 研究了骨髓中性粒细胞的亡.
- 研究了素H3素化 (H3Cit) 局部化和再分配.
- 评估了GSDME损失对中性粒细胞亡和NETosis的影响.
主要成果:
- 线粒体和死亡受体通路诱导GSDME依赖的调动和膜透.
- 这一过程导致H3Cit,DNA挤出和细胞质形成在apoptotic中性粒细胞.
- GSDME对于核和等离子体膜的破坏至关重要,为NETosis开启中性粒细胞.
结论:
- 亡信号使中性粒细胞中的PAD4参与,使其为NETosis做好准备.
- 由GSDME介导的膜破坏对于启动apoptotic中性粒细胞中网症至关重要.
- 这重新定义了中性粒细胞的终端分化作为一个依赖于GSDME的过程.
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