Epithelium-derived Cystatin-SN enhances eosinophil activation and infiltration via interleukin-5 in chronic rhinosinusitis with nasal polyps.

Abstract Background The interaction between epithelial cells and immune cells plays an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the mechanism/s underlying TH-biased inflammation in this process is/are largely unknown. Profiling protein expression in CRSwNP by shotgun proteomics suggested that Cystatin SN (CST1), a type 2 cysteine protease inhibitor, may play a role, as this was expressed with greatest difference in eosinophilic (E)CRSwNP and nonECRSwNP patients. Objectives To investigate the expression and role of CST1 in modulating eosinophilic inflammation in CRSwNP. Methods Sinonasal tissues were collected from 192 ECRSwNP, 52 nonECRSwNP and 40 control subjects. CST1 mRNA expression, localization, and concentration in the tissues were measured by real-time PCR, in situ hybridization, immunohistochemistry, and Elisa assay. Recombinant Cystatin SN was used to further explore the function of the molecule in dispersed nasal polyp cells and eosinophils extracted from polyp tissues and peripheral blood. Results CST1 was mainly expressed by epithelial cells, and significantly increased in ECRSwNP, but decreased in nonECRSwNP, compared with control subjects. CST1 expression was further increased in ECRSwNP with comorbid asthma and correlated with percentage of eosinophils in tissue samples. CST1 was induced by IL-4 and IL-13 in both ECRSwNP and nonECRSwNP tissue, and repressed by IL-17A in nonECRSwNP in the presence of neutrophils. CST1 enhanced eosinophil activation and recruitment by induction of interleukin-5 (IL-5). Conclusion Epithelium-derived CST1 modulates eosinophil activation and recruitment, the expression of which could be regulated by TH2 and TH17 cytokines.