Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, London, UK.
Centre for Rheumatology Research, Division of Medicine, University College London, London, UK.
Sci Rep. 2024 Jun 6;14(1):13074. doi: 10.1038/s41598-024-62325-3.
While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
虽然适应性免疫反应在系统性红斑狼疮（SLE）中已被广泛研究，但关于自然杀伤（NK）细胞对疾病发病机制的贡献，证据有限且相互矛盾。关于 NK 细胞在更严重的青少年发病（J）SLE 表型中的作用，证据则更少。在这项研究中，对一大群 J 型 SLE 患者的 NK 细胞表型和功能进行分析表明，与年龄和性别匹配的健康对照组相比，J 型 SLE 患者的总 NK 细胞以及表达穿孔素和颗粒酶 A 的 NK 细胞群体明显减少。NK 细胞频率的降低与疾病活动度增加有关，来自活动期和低疾病活动期 J 型 SLE 患者与健康对照组的 NK 细胞群体的转录组分析证实，疾病活动度是 NK 细胞基因表达差异的主要驱动因素。差异表达基因的通路分析显示，与健康对照组相比，在活动期疾病中干扰素-α反应上调，细胞外排作用下调。进一步的基因集富集分析还表明，在活动期疾病中凋亡途径的代表性过高。这表明，在 J 型 SLE 中，凋亡倾向增加可能是导致 NK 细胞缺乏的一个潜在因素。
