Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, USA.
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Semin Immunol. 2014 Apr;26(2):114-26. doi: 10.1016/j.smim.2014.02.003. Epub 2014 Mar 1.
Bone marrow-derived natural killer (NK) cells constitute the major subset of cytotoxic lymphocytes in peripheral blood. They provide innate defense against intracellular infection or malignancy and contribute to immune homeostasis. Large numbers of NK cells are also present in tissues, including the liver and uterus, where they can mediate immunosurveillance but also play important roles in tissue remodeling and vascularization. Here, we review the pathways involved in NK cell lineage commitment and differentiation, discussing relationships to other lymphocyte populations and highlighting genetic determinants. Characterizing NK cells from distinct tissues and during infections have revealed subset specializations, reflecting inherent cellular plasticity. In this context, we discuss how different environmental and inflammatory stimuli may shape NK cells. Particular emphasis is placed on genes identified as being critical for NK cell development, differentiation, and function from studies of model organisms or associations with disease. Such studies are also revealing important cellular redundancies. Here, we provide a view of the genetic framework constraining NK cell development and function, pinpointing molecules required for these processes but also underscoring plasticity and redundancy that may underlie robust immunological function. With this view, built in redundancy may highlight the importance of NK cells to immunity.
骨髓来源的自然杀伤 (NK) 细胞构成外周血中细胞毒性淋巴细胞的主要亚群。它们提供针对细胞内感染或恶性肿瘤的先天防御，并有助于免疫稳态。大量的 NK 细胞也存在于组织中，包括肝脏和子宫，在这些组织中，它们可以介导免疫监视，但也在组织重塑和血管生成中发挥重要作用。在这里，我们回顾了 NK 细胞谱系定向和分化所涉及的途径，讨论了与其他淋巴细胞群的关系，并强调了遗传决定因素。对来自不同组织和感染期间的 NK 细胞进行的特征描述揭示了亚群的特化，反映了固有细胞的可塑性。在这种情况下，我们讨论了不同的环境和炎症刺激如何塑造 NK 细胞。特别强调了从模式生物研究或与疾病的关联中确定的对 NK 细胞发育、分化和功能至关重要的基因。这些研究也揭示了重要的细胞冗余性。在这里，我们提供了一个约束 NK 细胞发育和功能的遗传框架的观点，指出了这些过程所需的分子，但也强调了可能为强大的免疫功能提供基础的可塑性和冗余性。从这个角度来看，内置冗余性可能突出了 NK 细胞对免疫的重要性。
