Gene expression changes in house dust mite-induced allergy: From mouse model to human asthma

Asthma is a heterogeneous disease characterized by diverse immune and inflammatory phenotypes driven by complex interactions among multiple cell types. To investigate the temporal transcriptional programs associated with chronic allergen exposure and their relevance to human asthma, we performed a time-series transcriptomic analysis of lung tissue from a mouse model subjected to repeated intranasal exposure to Dermatophagoides pteronyssinus (Der.p), and integrated these findings with peripheral blood mononuclear cell (PBMC) transcriptomes from two independent asthma cohorts. Mice were subjected to repeated Der.p exposure, and lung transcriptomes were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified and grouped into distinct temporal expression patterns using k-means clustering. Functional enrichment analysis of temporally consistent gene clusters showed sustained activation of immune and inflammatory pathways, with concurrent suppression of pathways related to tissue organization. Co-expression network analysis further identified Dipk2a and Specc1l as central nodes within gene modules associated with chronic inflammation. To evaluate whether genes identified in the mouse model are also associated with asthma, these genes were examined in PBMC transcriptomes from Der.p–sensitized asthma patients in the COREA and PRISM cohorts. Directionally consistent expression changes were observed for subsets of genes in both cohorts, with SIGLEC1 and TRIM54 identified in both datasets. Together, this study delineates time-dependent transcriptional programs associated with chronic allergen-induced airway inflammation and identifies immune-related genes linked to asthma. The identified genes, including SIGLEC1 and TRIM54, represent candidate markers associated with chronic inflammatory responses in asthma and warrant further investigation. • Asthma is a complex disease influenced by genetic and environmental factors. • Genetic signatures were identified in both a mouse model and patients with asthma. • Chronic inflammation was associated with candidate genes and potential biomarkers. • Key genes linking lung tissue and peripheral blood were identified. • These findings provide insights into asthma pathogenesis and potential therapeutic targets.