Role of Polo-like kinase 1 in T2-low asthma model

<bold>Background:</bold> Non-type 2 (T2-low) asthma is a major component of severe asthma, drawing attention due to its distinct cytokine profile from type 2 (T2-high) asthma and insensitivity to conventional treatments. Polo-like kinase 1 (PLK1) plays an important role in cell proliferation and contraction. <bold>Objective:</bold> To identify the change of PLK1 expression in T2-low asthma model and validate its role in T2-low asthma. <bold>Results:</bold> PLK1 expression was significantly increased in lung tissues of the T2-low asthma model. Specific inhibition of PLK1 blocked sphingosine 1-phosphate (S1P) induced proliferation and contraction of airway smooth muscle cells in vitro. Application of PLK1-specific inhibitors volasertib significantly alleviated airway inflammation, airway remodeling (thickening of the airway smooth muscle layer and collagen deposition) and airway hyperresponsiveness. It also improved the function of both large and small airway function in the T2-low asthma model, with varying degrees of improvement observed in FEV25/FVC, FEV50/FVC, MMEF, FEF50 and FEF75. Inhibition of PLK1 significantly reduced the levels of IL-5, IL-6, IL-17A and IL-21 in BALF of T2-low asthma model, but had little effect on IL-4 and IL-13, which may act through Th17-related pathway and part of T2-related pathway. <bold>Conclusion:</bold> PLK1 is expected to be a potential target for the treatment of T2-low asthma by improving airway inflammation, airway remodeling and airway hyperresponsiveness.