Neutrophils are key inflammatory cells in the immunopathogenesis of asthma. Neutrophil migration can be initiated through activation of the CXCR1 and CXCR2 receptors by CXC chemokines, such as IL-8. Although transcription factor KLF2 has been found to maintain T cell migration patterns through repression of several chemokine receptors, whether KLF2 can regulate neutrophil migration via modulation of CXCR1 and CXCR2 is unknown. Here, we aimed to explore the functions of KLF2, CXCR1 and CXCR2 in neutrophil migration in asthma and to establish a regulatory role of KLF2 for CXCR1/2. We demonstrate that with asthma aggravation, the percentages and migration rates of peripheral blood neutrophils gradually increased in asthmatic patients and the guinea pig asthma model. Correspondingly, both the KLF2 mRNA and protein levels in neutrophils were gradually reduced. While CXCR1 and CXCR2 expression was negatively correlated with KLF2. In vitro knockdown of KLF2 dramatically increased the migration of HL-60-drived neutrophil-like cells, which was accompanied by an increase in the CXCR1 and CXCR2 mRNA and protein expression levels. Taken together, our results indicate that decreased KLF2 aggravates asthma progression by promoting neutrophil migration, which is associated with the transcriptional upregulation of CXCR1 and CXCR2. The KLF2 and/or CXCR1/2 expression levels may represent an indicator of asthma severity.

中性粒细胞是哮喘免疫发病机制中的关键炎症细胞。中性粒细胞迁移可通过CXC趋化因子（例如IL-8）激活CXCR1和CXCR2受体而引发。尽管已经发现转录因子KLF2通过抑制几种趋化因子受体来维持T细胞迁移模式，但是KLF2是否可以通过调节CXCR1和CXCR2来调节嗜中性粒细胞迁移尚不清楚。在这里，我们旨在探讨KLF2，CXCR1和CXCR2在哮喘中性粒细胞迁移中的功能，并确定KLF2对CXCR1 / 2的调节作用。我们证明，随着哮喘的加重，哮喘患者和豚鼠哮喘模型中外周血中性粒细胞的百分比和迁移率逐渐增加。相应地，中性粒细胞中的KLF2 mRNA和蛋白质水平均逐渐降低。CXCR1和CXCR2表达与KLF2负相关。KLF2的体外敲除显着增加了HL-60驱动的嗜中性粒细胞样细胞的迁移，并伴有CXCR1和CXCR2 mRNA和蛋白质表达水平的增加。两者合计，我们的结果表明，减少的KLF2通过促进嗜中性粒细胞迁移而加重哮喘的进展，这与CXCR1和CXCR2的转录上调有关。KLF2和/或CXCR1 / 2表达水平可能代表哮喘严重程度。这伴随着CXCR1和CXCR2 mRNA和蛋白质表达水平的增加。两者合计，我们的结果表明，减少的KLF2通过促进嗜中性粒细胞迁移而加重哮喘的进展，这与CXCR1和CXCR2的转录上调有关。KLF2和/或CXCR1 / 2表达水平可能代表哮喘严重程度。这伴随着CXCR1和CXCR2 mRNA和蛋白质表达水平的增加。两者合计，我们的结果表明，减少的KLF2通过促进嗜中性粒细胞迁移而加重哮喘的进展，这与CXCR1和CXCR2的转录上调有关。KLF2和/或CXCR1 / 2表达水平可能代表哮喘严重程度。