集成的NLRP3,AIM2,NLRC4,皮林炎酶激活和组装驱动PANoptosis
SuHyeon Oh1, Jihye Lee1, Jueun Oh1
1Department of Biological Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
Cellular & molecular immunology
|November 26, 2023
概括
多个炎症体传感器合作触发编程细胞死亡,形成驱动炎症的细胞外复合体. 这一发现揭示了对先天免疫和潜在的治疗点至关重要的新相互作用.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 炎症细胞是重要的先天性免疫哨兵,可以感知病原体和损伤,调解炎症,发育和癌症.
- 炎症酶激活涉及传感器与病原体和损伤相关的分子模式 (PAMP / DAMP) 结合,与ASC和caspase-1形成复合体.
- 多个炎症体的协同激活在疾病期间发生,但整合这些传感器用于宿主防御的机制尚不清楚.
研究的目的:
- 阐明集成多个炎酶体传感器以实现最佳宿主防御的分子机制.
- 为了研究由多个连接体同时激活炎酶的后果.
- 识别由多个炎症体传感器组成的复合体的组件和功能.
主要方法:
- 使用多个连接体同时激活炎症体.
- 编程炎症细胞死亡类型的分析.
- 同免疫沉和质谱测量用于识别多蛋白质复合体的组成部分.
- 细胞外炎症组合体的表征.
主要成果:
- 通过多个连接体同时激活诱导独特的编程炎症细胞死亡,而不是通过单个连接体模仿.
- 确定了NLRP3,AIM2,NLRC4和Pyrin在一个大型多蛋白复合体内,包括ASC,caspase-1,caspase-8和RIPK3,驱动PANoptosis.
- 这种多蛋白质复合体在细胞外释放为多个炎症体,能够在巨细胞吸收后诱导炎症.
结论:
- 发现了一种新的调节连接和炎症体传感器之间的分子相互作用.
- 这些相互作用驱动了多蛋白质复合体的组装,集成了多个炎症体传感器和细胞死亡调节器.
- 这些发现在炎症体生物学中建立了一个新的范式,突出了NLRP3,AIM2,NLRC4和Pyrin之间的关键相互作用,并提供了新的治疗点.
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