Natural killer (NK) cells are innate lymphocytes that exhibit adaptive features, such as clonal expansion and memory, during viral infection. Although activating receptor engagement and proinflammatory cytokines are required to drive NK cell clonal expansion, additional stimulatory signals controlling their proliferation remain to be discovered. Here, we describe one such signal that is provided by the adrenergic nervous system, and demonstrate that cell-intrinsic adrenergic signaling is required for optimal adaptive NK cell responses. Early during mouse cytomegalovirus (MCMV) infection, NK cells up-regulated Adrb2 (which encodes the β2-adrenergic receptor), a process dependent on IL-12 and STAT4 signaling. NK cell–specific deletion of Adrb2 resulted in impaired NK cell expansion and memory during MCMV challenge, in part due to a diminished proliferative capacity. As a result, NK cell-intrinsic adrenergic signaling was required for protection against MCMV. Taken together, we propose a novel role for the adrenergic nervous system in regulating circulating lymphocyte responses to viral infection.

中文翻译：

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细胞固有的肾上腺素信号传导控制 NK 细胞对病毒感染的适应性反应

自然杀伤 (NK) 细胞是先天性淋巴细胞，在病毒感染期间表现出适应性特征，例如克隆扩张和记忆。尽管驱动 NK 细胞克隆扩张需要激活受体结合和促炎细胞因子，但控制其增殖的其他刺激信号仍有待发现。在这里，我们描述了一种由肾上腺素能神经系统提供的信号，并证明细胞固有的肾上腺素能信号传导是最佳适应性 NK 细胞反应所必需的。在小鼠巨细胞病毒 (MCMV) 感染早期，NK 细胞上调 Adrb2（编码 β2 肾上腺素受体），这一过程依赖于 IL-12 和 STAT4 信号传导。NK 细胞特异性删除 Adrb2 会导致 MCMV 攻击期间 NK 细胞的扩增和记忆受损，部分原因是增殖能力减弱。因此，NK 细胞固有的肾上腺素信号传导对于预防 MCMV 是必需的。综上所述，我们提出肾上腺素能神经系统在调节循环淋巴细胞对病毒感染的反应中的新作用。