Decreased desmoplakin expression on bronchial epithelial cells promotes eosinophil transmigration in asthma

<bold>Background:</bold> Eosinophil infiltration to the airway is an important pathological manifestation of asthma. We tested whether eosinophil infiltration during airway inflammation was associated with the degradation of desmoplakin (DSP) a crucial component of desmosomes. <bold>Methods:</bold> Eosinophil count in BALF, DSP expression and desmosome structure in the bronchial epithelium was detected in an eosinophilic mouse model of asthma. The role of DSP in epithelial barrier function and its modulation by major basic protein (MBP) were studied in vitro. DSP mRNA in bronchial brushes from the U-BIOPRED asthma cohort was analyzed. <bold>Results:</bold> In the mouse asthma model, DSP expression was down-regulated and negatively correlated with BALF eosinophil count. Anti-IL-5 treatment in vivo alleviated DSP and eosinophil changes. MBP down-regulated DSP expression and barrier function in 16HBE cells. DSP knockdown reduced epithelial barrier function, as determined by transepithelial electric resistance, permeability to fluorescein isothiocyanate-dextran, and eosinophil transepithelial migration. Damaged desmosomes were observed by transmission electron microscopy. DSP mRNA was reduced in patients with severe asthma, and this correlated inversely with eosinophil count. DSP was decreased in serum of asthmatic patients compared with healthy controls (0.92±0.09 ng/mL vs. 1.95±0.27 ng/mL, p<0.001). <bold>Conclusion:</bold> In eosinophilic asthma inflammation, eosinophils may inhibit DSP expression in bronchial epithelial cells (BECs) and impair desmosome structures by releasing the granule protein MBP enabling transmigration into the airway.