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

Background 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. Recent evidence suggests that Krüppel-like factor 2 (KLF2), a transcription factor associated with susceptibility to SLE, is likely to be a potential therapeutic target for SLE. Methods This study focused on the role of KLF2 in the regulation of neutrophil apoptosis and its association with SLE disease activity. First, the expression of KLF2 in neutrophils of SLE was detected by real-time PCR and western blotting. The apoptosis levels and caspase3 mRNA levels in neutrophils from SLE patients and healthy controls were detected and analyzed. The correlation between KLF2 mRNA levels and apoptosis was analyzed. neutrophils from Health controls (HCs) were cultured in RPMI 1640 medium containing the KLF2 inhibitor Geranylgeranyl pyrophosphate (GGPP) or the KLF2 inducer geranylgeranyl transferase inhibitor (GGTI-298), and then the KLF2 levels and the apoptosis levels were detected in neutrophils. Lastly, neutrophils from HCs were cultured in RPMI 1640 medium containing sera from SLE patients, followed by the detection of KLF2 mRNA levels and apoptosis levels of neutrophils. Then, the correlation between KLF2 mRNA levels and SLE disease activity index (SLEDIA) was analyzed. Results It was shown that the expression of KLF2 in neutrophils of SLE patients is significantly suppressed, and the decreased KLF2 is 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 SLEDIA. In addition, we found that serum from SLE patients could induce apoptosis in neutrophils by down-regulating the expression of KLF2. Conclusion In summary, we revealed for the first time that KLF2 can regulate the apoptosis of neutrophils in this study. Moreover, our research showed that the KLF2 levels in neutrophils are closely related to the disease activity of SLE, which suggests that KLF2 in neutrophils may be involved in the occurrence and development of SLE.