KLF2控制中性粒细胞的凋亡，并与系统性红斑狼疮的疾病活动性有关

IF 4.9 2区医学 Q1 Medicine

Arthritis Research & Therapy Pub Date : 2024-12-19 DOI:10.1186/s13075-024-03461-z

Hongshuai Zhao, Zaichuan Lin, Peiwen Zhang, Jiayue Rao, Shumin Xu, Qing Luo, Junming Li

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引用次数: 0

摘要

中性粒细胞减少症在系统性红斑狼疮（SLE）患者中更为常见，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中性粒细胞减少的重要原因。然而，中性粒细胞凋亡增加在SLE中的具体机制尚不清楚。本研究的重点是kr ppel样因子2 （KLF2）在中性粒细胞凋亡调控中的作用及其与SLE疾病活度的关系。采用RT-PCR和western blot检测SLE患者和健康对照（hc）中性粒细胞中KLF2的水平。分析SLE患者KLF2水平与中性粒细胞凋亡水平的关系。采用KLF2抑制剂Geranylgeranyl焦磷酸（GGPP）和KLF2诱导剂Geranylgeranyl transferase inhibitor （GGTI-298）与中性粒细胞孵育，研究KLF2在中性粒细胞凋亡调控中的作用。为明确SLE患者血清是否影响中性粒细胞KLF2表达和凋亡，收集SLE患者血清，与hc中性粒细胞孵育，检测中性粒细胞KLF2水平和凋亡水平。此外，我们还分析了KLF2水平与SLE疾病活动指数（SLEDAI）的相关性。SLE患者中性粒细胞中KLF2的表达被显著抑制，KLF2的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、抗smith抗体阳性的SLE患者KLF2表达水平较低。此外，我们证明了调节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控制中性粒细胞的凋亡并与SLEDAI相关，提示中性粒细胞中的KLF2可能参与SLE的发生和发展。

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KLF2 controls the apoptosis of neutrophils and is associated with disease activity of systemic lupus erythematosus

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.

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来源期刊

Arthritis Research & Therapy RHEUMATOLOGY-

CiteScore

8.60

自引率

2.00%

发文量

261

审稿时长

14 weeks

期刊介绍： Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.