Neutropenia is more common in patients with systemic lupus erythematosus (SLE) and is a major cause of life-threatening infections. The increased apoptosis of neutrophils is likely to be an essential cause of neutropenia in SLE. However, the detailed mechanisms of increased neutrophil apoptosis in SLE remain unknown. This study focused on the role of Krüppel-like factor 2 (KLF2) in the regulation of neutrophil apoptosis and its association with SLE disease activity. The levels of KLF2 in neutrophils from SLE patients and healthy controls (HCs) were detected by RT-PCR and western blot. The relationship between the levels of KLF2 and the apoptosis levels of neutrophils in SLE patients was analyzed. The KLF2 inhibitor Geranylgeranyl pyrophosphate (GGPP) and the KLF2 inducer geranylgeranyl transferase inhibitor (GGTI-298) were used to incubate with neutrophils to investigate the role of KLF2 in the regulation of neutrophil apoptosis. To clarify whether serum from SLE patients affects neutrophil KLF2 expression and apoptosis, sera from SLE patients were collected and used to incubate with neutrophils from HCs, followed by the detection of KLF2 levels and apoptosis levels of neutrophils. Additionally, the correlation between KLF2 levels and SLE disease activity index (SLEDAI) was analyzed. The expression of KLF2 in neutrophils of SLE patients was significantly suppressed, and the decreased KLF2 was associated with the upregulation of neutrophil apoptosis. Moreover, newly diagnosed SLE patients, SLE patients with higher serum IgG and positive anti-Smith antibodies had lower KLF2 expression. Furthermore, we demonstrated that modulating the expression of KLF2 can regulate the apoptosis of neutrophils. The levels of KLF2 in neutrophils were associated with the SLEDAI. In addition, we found that serum from SLE patients could induce apoptosis in neutrophils by down-regulating the expression of KLF2. KLF2 controls the apoptosis of neutrophils and is associated with SLEDAI, which suggests that KLF2 in neutrophils may be involved in the occurrence and development of SLE.

中文翻译：

---

KLF2 控制中性粒细胞凋亡，并与系统性红斑狼疮的疾病活动有关。


中性粒细胞减少症在系统性红斑狼疮 （SLE） 患者中更常见，是危及生命的感染的主要原因。中性粒细胞凋亡增加可能是 SLE 中性粒细胞减少症的重要原因。然而，SLE 中性粒细胞凋亡增加的详细机制仍然未知。本研究侧重于 Krüppel 样因子 2 （KLF2） 在中性粒细胞凋亡调节中的作用及其与 SLE 疾病活动的关系。RT-PCR 和 western blot 检测 SLE 患者和健康对照者 （HCs） 中中性粒细胞中 KLF2 水平。分析 SLE 患者 KLF2 水平与中性粒细胞凋亡水平的关系。使用 KLF2 抑制剂香叶基香叶酰焦磷酸酯 （GGPP） 和 KLF2 诱导剂香叶基香叶酰转移酶抑制剂 （GGTI-298） 与中性粒细胞孵育，探讨 KLF2 在中性粒细胞凋亡调节中的作用。为了阐明 SLE 患者血清是否影响中性粒细胞 KLF2 的表达和细胞凋亡，收集 SLE 患者的血清并与 HCs 的中性粒细胞孵育，然后检测中性粒细胞的 KLF2 水平和细胞凋亡水平。此外，还分析了 KLF2 水平与 SLE 疾病活动指数 （SLEDAI） 之间的相关性。SLE 患者中性粒细胞中 KLF2 的表达受到显著抑制，KLF2 降低与中性粒细胞凋亡的上调有关。此外，新诊断的 SLE 患者、血清 IgG 较高且抗 Smith 抗体阳性的 SLE 患者 KLF2 表达较低。此外，我们证明调节 KLF2 的表达可以调节中性粒细胞的凋亡。中性粒细胞中 KLF2 的水平与 SLEDAI 相关。 此外，我们发现 SLE 患者血清可通过下调 KLF2 的表达诱导中性粒细胞凋亡。KLF2 控制中性粒细胞凋亡并与 SLEDAI 相关，这表明中性粒细胞中的 KLF2 可能参与 SLE 的发生和发展。