Natural killer (NK) cells are innate immune lymphocytes with potent cytolytic and immune-regulatory activities. NK cells are well-known for their ability to kill infected and malignant cells in a fast and non-specific way without prior sensitization. For this purpose, NK cells are equipped with a set of cytotoxic molecules such as perforin and apoptosis-inducing proteins. NK cells also have the capacity to produce large amounts of cytokines and chemokines that synergize with their cytotoxic function and that ensure interaction with other immune cells. A less known feature of NK cells is their capacity to kill non-infected autologous cells, such as immature dendritic cells and activated T cells and monocytes. Via the release of large amounts of TNF-α and IFN-γ, NK cells may contribute to disease pathology. Conversely they may exert a regulatory role through secretion of immuno-regulatory cytokines such as GM-CSF, IL-13, and IL-10. Thus, NK cells may be important target and effector cells in the pathogenesis of autoinflammatory diseases, in particular in those disorders associated with a cytokine storm or in conditions where immune cells are highly activated. Key examples of such diseases are systemic juvenile idiopathic arthritis (sJIA) and its well-associated complication, macrophage activation syndrome (MAS). sJIA is a chronic childhood immune disorder of unknown etiology, characterized by arthritis and systemic inflammation, including a daily spiking fever and evanescent rash. MAS is a potentially fatal complication of autoimmune and autoinflammatory diseases, and most prevalently associated with sJIA. MAS is considered as a subtype of hemophagocytic lymphohistiocytosis (HLH), a systemic hyperinflammatory disorder characterized by defective cytotoxic pathways of cytotoxic T and NK cells. In this review, we describe the established features of NK cells and provide the results of a literature survey on the reported NK cell abnormalities in monogenic and multifactorial autoinflammatory disorders. Finally, we discuss the role of NK cells in the pathogenesis of sJIA and MAS.

天然杀伤（NK）细胞是具有强大的细胞溶解和免疫调节活性的先天免疫淋巴细胞。NK细胞以无需事先致敏的快速和非特异性方式杀死感染和恶性细胞的能力而闻名。为此，NK细胞配备了一组细胞毒性分子，例如穿孔素和凋亡诱导蛋白。NK细胞还具有产生大量细胞因子和趋化因子的能力，这些细胞因子和趋化因子与其细胞毒性功能协同作用并确保与其他免疫细胞的相互作用。NK细胞的一个鲜为人知的特征是其杀死未感染的自体细胞（例如未成熟的树突状细胞以及活化的T细胞和单核细胞）的能力。通过释放大量的TNF-α和IFN-γ，NK细胞可能有助于疾病病理。相反，它们可能通过分泌免疫调节细胞因子（例如GM-CSF，IL-13和IL-10）发挥调节作用。因此，NK细胞在自身炎性疾病的发病机理中，特别是在与细胞因子风暴有关的那些疾病中或在免疫细胞被高度活化的情况下，可能是重要的靶标和效应细胞。这类疾病的主要例子是系统性幼年特发性关节炎（sJIA）及其相关的并发症巨噬细胞活化综合征（MAS）。sJIA是一种病因不明的儿童慢性免疫性疾病，其特征在于关节炎和全身性炎症，包括每天的尖峰热和e疹。MAS是自身免疫性疾病和自身炎症性疾病的潜在致命并发症，最常见于sJIA。MAS被认为是吞噬性淋巴细胞组织细胞增生症（HLH）的一种亚型，它是一种系统性过度炎症性疾病，其特征在于细胞毒性T细胞和NK细胞的细胞毒性途径缺陷。在这篇综述中，我们描述了NK细胞的既定特征，并提供了关于单基因和多因素自发性炎症疾病中报道的NK细胞异常的文献调查结果。最后，我们讨论了NK细胞在sJIA和MAS发病机理中的作用。