NK细胞受体NKp46在ER压力细胞上识别ecto-calreticulin
Sumit Sen Santara1,2,3, Dian-Jang Lee1,2, Ângela Crespo1,2
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Nature
|April 5, 2023
概括
自然杀手细胞使用NKp46来识别应激细胞上的外部化卡尔雷蒂库林 (ecto-CRT). 这种相互作用触发NK细胞信号和杀死,对于消除化疗诱导的细胞死亡和瘤至关重要.
科学领域:
- 免疫学
- 细胞生物学
- 癌症研究
背景情况:
- 自然杀手 (NK) 细胞通过激活受体消除受感染,转变或应激的细胞.
- NKp46是大多数NK细胞和一些先天性淋巴细胞的关键激活受体.
- 对NKp46的内源性连接体尚未确定.
研究的目的:
- 为了确定NKp46受体的内源配体.
- 阐明NKp46- 连接物相互作用在NK细胞中介细胞毒性的作用.
- 研究针对癌症和疾病这种相互作用的治疗潜力.
主要方法:
- 在内等质网膜 (ER) 应激过程中研究NKp46外化卡莱蒂库林 (ecto- CRT) 的识别.
- 使用基因淘汰/淘汰CALR和抗体阻断来评估NKp46的功能.
- 使用黑色素瘤和肺癌的小鼠模型来评估NKp46介导的瘤控制.
主要成果:
- 在ER应激过程中,NKp46直接识别ecto-CRT,并转移到细胞表面.
- 癌细胞,病毒感染细胞和衰老细胞的NKp46介导杀死依赖于ecto- CRT.
- NKp46-ecto-CRT相互作用增强抗瘤免疫力,包括NK细胞降粒和细胞因子分泌 in vivo.
结论:
- NKp46将ecto-CRT识别为与危险相关的分子模式 (DAMP).
- 这种识别途径对于消除ER压力细胞至关重要,并有助于抗瘤免疫力.
- 针对NKp46-ecto-CRT轴是癌症免疫治疗的一个有希望的策略.
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