Department of Oncology UNIL CHUV, University of Lausanne, Ch. des Boveresses 155, 1066, Epalinges, Switzerland.
Cell Mol Life Sci. 2018 Sep;75(18):3371-3379. doi: 10.1007/s00018-018-2865-1. Epub 2018 Jun 29.
Natural killer (NK) cells are innate cytotoxic effector cells that play important protective roles against certain pathogens as well as against pathogen-infected and transformed host cells. NK cells continuously arise from adult bone marrow-resident haematopoietic progenitors. Their generation can be sub-divided into three phases. The early NK cell development phase from multipotent common lymphoid progenitors occurs at least in part in common with that of additional members of a family of innate lymphoid cells, for which NK cells are the founding member. An intermediate phase of NK cell differentiation is characterized by the acquisition of IL-15 responsiveness and lineage-defining properties such as the transcription of genes coding for cytotoxic effector molecules. This is followed by a late maturation phase during which NK cells lose homeostatic expansion and increase effector capacity. These three phases are regulated by multiple stage-specific but not NK cell-specific transcription factors. This review summarizes the NK cell developmental and maturation processes and their transcriptional regulation with an emphasis on data derived from genetically modified mouse models.
自然杀伤 (NK) 细胞是先天的细胞毒性效应细胞，在抵抗某些病原体以及受病原体感染和转化的宿主细胞方面发挥着重要的保护作用。NK 细胞源源不断地产生于成人骨髓常驻造血祖细胞。其生成可以分为三个阶段。多能共同淋巴样祖细胞中的早期 NK 细胞发育阶段至少部分与先天淋巴样细胞家族的其他成员的发生是共同的，而 NK 细胞是该家族的创始成员。NK 细胞分化的中间阶段的特征是获得 IL-15 反应性和谱系定义特性，例如编码细胞毒性效应分子的基因的转录。随后是晚期成熟阶段，在此期间 NK 细胞失去了稳态扩增并增加了效应能力。这三个阶段受到多种阶段特异性而非 NK 细胞特异性转录因子的调节。本文综述了 NK 细胞的发育和成熟过程及其转录调控，重点介绍了来自基因修饰小鼠模型的数据。
