Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University Alpert Medical School, Providence, RI 02912, USA.
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Avenue de Luminy, 13288 Marseille, France; Department of Immunology, IRCSS Bambino Gesù Children's Hospital, Rome, Italy.
Cell Rep. 2020 Jul 7;32(1):107855. doi: 10.1016/j.celrep.2020.107855.
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.
肝脏中存在两种主要的固有淋巴细胞 (ILC) 群体：常规自然杀伤 (cNK) 细胞和组织驻留 NK (trNK) 细胞。利用 MCMV 感染模型，我们发现，与肝 cNK 细胞不同，trNK 细胞最初经历收缩阶段，然后恢复到稳态水平。收缩与 MCMV 无关，因为在 poly(I:C)/CpG 或 α-GalCer 注射后也观察到类似的表型。快速收缩阶段是由于细胞凋亡引起的，而恢复阶段则通过原位增殖发生。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症细胞因子诱导的。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 NK 细胞区室的独特特性。
