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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46
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Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46

机译：通过NKp46鉴定，激活和选择性体内消融小鼠NK细胞

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Natural killer (NK) cells contribute to a variety of innate immune responses to viruses, tumors and allogeneic cells. However, our understanding of NK cell biology is severely limited by the lack of consensus phenotypic definition of these cells across species, by the lack of specific marker to visualize them in situ, and by the lack of a genetic model where NK cells may be selectively ablated. NKp46/CD335 is an Ig-like superfamily cell surface receptor involved in human NK cell activation. In addition to human, we show here that NKp46 is expressed by NK cells in all mouse strains analyzed, as well as in three common monkey species, prompting a unifying phenotypic definition of NK cells across species based on NKp46 cell surface expression. Mouse NKp46 triggers NK cell effector function and allows the detection of NK cells in situ. NKp46 expression parallels cell engagement into NK differentiation programs because it is detected on all NK cells from the immature CD122~+NK1.1~+DX5~- stage and on a minute fraction of NK-like T cells, but not on CDId-restricted NKT cells. Moreover, human NKp46 promoter drives NK cell selective expression both in vitro and in vivo. Using NKp46 promoter, we generated transgenic mice expressing EGFP and the diphtheria toxin (DT) receptor in NK cells. DT injection in these mice leads to a complete and selective NK cell ablation. This model paves a way for the in vivo characterization and preclinical assessment of NK cell biological function.
机译：天然杀伤（NK）细胞有助于对病毒，肿瘤和同种异体细胞的各种先天免疫应答。但是，我们对NK细胞生物学的理解受到以下严重限制：缺乏跨物种的这些细胞的共有表型定义，缺乏在原位可视化它们的特异性标记以及缺乏可以选择性地选择NK细胞的遗传模型消融了。 NKp46 / CD335是涉及人类NK细胞活化的Ig样超家族细胞表面受体。除人类外，我们在这里显示，NKp46在所有分析的小鼠品系以及三种常见的猴子物种中均由NK细胞表达，这促使基于NKp46细胞表面表达跨物种的NK细胞具有统一的表型定义。小鼠NKp46触发NK细胞效应子功能，并允许原位检测NK细胞。 NKp46的表达使细胞参与NK分化程序，因为它在未成熟的CD122〜+ NK1.1〜+ DX5〜阶段的所有NK细胞上以及一小部分的NK样T细胞中都被检测到，但在CDId限制下却未检测到NKT细胞。而且，人NKp46启动子在体外和体内都驱动NK细胞选择性表达。使用NKp46启动子，我们生成了在NK细胞中表达EGFP和白喉毒素（DT）受体的转基因小鼠。在这些小鼠中进行DT注射会导致NK细胞完全选择性的消融。该模型为NK细胞生物学功能的体内表征和临床前评估铺平了道路。

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