LAUSR

House dust mites (HDM) can cause DNA double‐strand breaks in the lungs of asthmatic patients. However, the molecular mechanisms driving DNA damage and repair in HDM‐induced asthma are yet to be elucidated. Thus, in this study, HDM treatment was applied to BEAS‐2B cells and mice to mimic the pathological process of asthma in vitro and in vivo, respectively. γ‐H2AX foci and expression were measured by immunofluorescence staining and western blot, respectively. The levels of interleukin (IL)‐4, IL‐6, IL‐13, and tumour necrosis factor α (TNFα) were measured using enzyme‐linked immunoassay. The expression of USP25 and BARD1 was measured by reverse transcription quantitative PCR and western blot. Co‐immunoprecipitation and ubiquitination assays were employed to detect the relationship between USP25 and BARD1. As per the results, it was found that the deubiquitylating enzyme USP25 repressed HDM‐induced DNA damage and the production of proinflammatory cytokines, including TNF‐α, IL‐4, IL‐8, and IL‐13, in BEAS‐2B cells; in contrast, the depletion of USP25 led to the opposite effects. USP25‐mediated inhibition of DNA damage and inflammation was facilitated by the stabilizing protein BARD1, which is a tumor suppressor that principally functions by promoting DNA repair and replication in BEAS‐2B cells. Furthermore, USP25 was found to robustly augment BARD1 protein abundance and prevent HDM‐induced DNA damage and inflammation in vivo. Taken together, these results suggest a novel mechanism contributing to DNA damage and repair in HDM‐induced asthma and that selectively modulating this pathway could lead to a novel therapeutic approach for controlling and managing asthma due to HDM exposure.