Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada.
Cell Mol Immunol. 2011 Jan;8(1):1-11. doi: 10.1038/cmi.2010.38. Epub 2010 Aug 16.
Natural killer (NK) cells are found in lymphoid and non-lymphoid organs. In addition to important roles in immune surveillance, some NK cells contribute to angiogenesis and circulatory regulation. The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites. In species with invasive hemochorial placentation, these uterine natural killer (uNK) cells, via secretion of cytokines, chemokines, mucins, enzymes and angiogenic growth factors, contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis. In humans, uNK cells have the phenotype CD56(bright)CD16(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy. Gene expression studies indicate that CD56(bright)CD16(dim) uterine and circulating cells are functionally distinct. In humans but not mice or other species with post-implantation decidualization, uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility. Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function, achieved via interferon (IFN)-γ secretion. During spiral arterial modification, branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict. The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance, high-volume channels. Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women. Here we briefly review key information concerning uNK cell functions from studies in rodents, summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized, pregnant mouse model for in vivo investigations of human uNK cell functions.
自然杀伤 (NK) 细胞存在于淋巴器官和非淋巴器官中。除了在免疫监视中发挥重要作用外，一些 NK 细胞还参与血管生成和循环调节。妊娠早期的子宫是非淋巴器官，富含特异性募集到胎盘附着部位的 NK 细胞。在具有侵袭性合胞胎盘的物种中，这些子宫自然杀伤 (uNK) 细胞通过分泌细胞因子、趋化因子、粘蛋白、酶和血管生成生长因子，有助于将中系膜子宫内膜变为称为蜕膜基底的独特基质环境。在人类中，uNK 细胞具有 CD56(bright)CD16(dim)的表型，并且在月经周期的晚期分泌期和妊娠早期大量出现。基因表达研究表明，CD56(bright)CD16(dim)子宫和循环细胞在功能上是不同的。在人类中，但不是在具有植入后蜕膜化的小鼠或其他物种中，uNK 细胞可能有助于胚胎着床，并且作为女性不孕的治疗靶点很有意义。在小鼠中的组织学和遗传学研究首先确定了触发妊娠螺旋动脉修饰过程是 uNK 细胞的主要功能之一，这是通过干扰素 (IFN)-γ 分泌来实现的。在螺旋动脉修饰过程中，穿过子宫内膜/蜕膜的子宫动脉分支暂时失去其肌层外套和收缩能力。随着这些血管扩张并成为低阻力、大容量通道，血管标志物的表达从动脉变为静脉。由于无法在孕妇中进行子宫内膜时间进程研究，因此很难全面了解人类 uNK 细胞的血管相互作用。在这里，我们简要回顾了从啮齿动物研究中获得的关于 uNK 细胞功能的关键信息，总结了关于人类 uNK 细胞的要点，并描述了我们在开发用于体内研究人类 uNK 细胞功能的人源化、妊娠小鼠模型方面的初步研究。
