Primary immunodeficiency diseases (PIDs) are rare diseases that are characterized by genetic mutations that damage immunological function, defense, or both. Some of these rare diseases are caused by aberrations in the normal development of natural killer cells (NKs) or affect their lytic synapse. The pathogenesis of these types of diseases as well as the processes underlying target recognition by human NK cells is not well understood. Utilizing induced pluripotent stem cells (iPSCs) will aid in the study of human disorders, especially in the PIDs with defects in NK cells for PID disease modeling. This, together with genome editing technology, makes it possible for us to facilitate the discovery of future therapeutics and/or cell therapy treatments for these patients, because, to date, the only curative treatment available in the most severe cases is hematopoietic stem cell transplantation (HSCT). Recent progress in gene editing technology using CRISPR/Cas9 has significantly increased our capability to precisely modify target sites in the human genome. Among the many tools available for us to study human PIDs, disease- and patient-specific iPSCs together with gene editing offer unique and exceptional methodologies to gain deeper and more thorough understanding of these diseases as well as develop possible alternative treatment strategies. In this review, we will discuss some immunodeficiency disorders affecting NK cell function, such as classical NK deficiencies (CNKD), functional NK deficiencies (FNKD), and PIDs with involving NK cells as well as strategies to model and correct these diseases for further study and possible avenues for future therapies.

中文翻译：

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治疗 NK 细胞缺陷引起的原发性免疫缺陷：从干细胞疗法到基因编辑

原发性免疫缺陷病 (PID) 是一种罕见疾病，其特征是基因突变会损害免疫功能和/或防御功能。其中一些罕见疾病是由自然杀伤细胞 (NK) 正常发育异常或影响其裂解突触引起的。这些类型疾病的发病机制以及人类 NK 细胞识别目标的过程尚不清楚。利用诱导多能干细胞 (iPSC) 将有助于研究人类疾病，特别是在 PID 疾病模型中 NK 细胞缺陷的 PID。这与基因组编辑技术一起，使我们能够促进针对这些患者的未来疗法和/或细胞疗法的发现，因为迄今为止，在最严重的病例中唯一可用的治疗方法是造血干细胞移植（造血干细胞移植）。使用 CRISPR/Cas9 的基因编辑技术的最新进展显着提高了我们精确修改人类基因组中目标位点的能力。在我们可用于研究人类 PID 的众多工具中，疾病和患者特异性 iPSC 与基因编辑相结合，提供了独特且卓越的方法，可以更深入、更彻底地了解这些疾病，并开发可能的替代治疗策略。在这篇综述中，我们将讨论一些影响 NK 细胞功能的免疫缺陷疾病，例如经典 NK 缺陷 (CNKD)、功能性 NK 缺陷 (FNKD) 和涉及 NK 细胞的 PID，以及建模和纠正这些疾病的策略以供进一步研究以及未来治疗的可能途径。