The liver harbors two main innate lymphoid cell (ILC) populations: conventional NK (cNK) cells and tissue-resident NK (trNK) cells. Using the MCMV model of infection, we find that, in contrast to liver cNK cells, trNK cells initially undergo a contraction phase followed by a recovery phase to homeostatic levels. The contraction is MCMV independent because a similar phenotype is observed following poly(I:C)/CpG or α-GalCer injection. The rapid contraction phase is due to apoptosis, whereas the recovery phase occurs via proliferation in situ. Interestingly, trNK cell apoptosis is not mediated by fratricide and not induced by liver lymphocytes or inflammatory cytokines. Instead, we find that trNK cell apoptosis is the consequence of an increased sensitivity to lactic acid. Mechanistic analysis indicates that trNK cell sensitivity to lactate is linked to impaired mitochondrial function. These findings underscore the distinctive properties of the liver-resident NK cell compartment.

肝脏含有两个主要的先天性淋巴样细胞 (ILC) 细胞群：常规 NK (cNK) 细胞和组织驻留 NK (trNK) 细胞。使用感染的 MCMV 模型，我们发现，与肝 cNK 细胞相比，trNK 细胞最初经历收缩阶段，然后是恢复阶段到稳态水平。收缩与 MCMV 无关，因为在 poly(I:C)/CpG 或 α-GalCer 注射后观察到类似的表型。快速收缩阶段是由于细胞凋亡，而恢复阶段是通过原位增殖发生的. 有趣的是，trNK 细胞凋亡不是由自相残杀介导的，也不是由肝淋巴细胞或炎性细胞因子诱导的。相反，我们发现 trNK 细胞凋亡是对乳酸敏感性增加的结果。机制分析表明，trNK 细胞对乳酸的敏感性与线粒体功能受损有关。这些发现强调了肝脏驻留的 NK 细胞区室的独特特性。