The functional role of CST1 and CCL26 in asthma development

Background: Asthma is the most common chronic disease in children with an increasing prevalence in recent years. Its development depends on genetic and environmental factors and allergic sensitization is a known trigger. Dog allergens affect up to 30% of all children and dog dander-sensitized children show increased expression of cystatin-1 (CST1) and eotaxin-3 (CCL26). The aim of our study was to investigate the functional mechanism of CST1 and CCL26 in the alveolar basal epithelial cell line A549. Methods: A549 cells were transfected with individual overexpression vectors for CST1 and CCL26 and RNA sequencing was performed to examine the transcriptomics. DESeq2 was used to identify differentially expressed genes (= DEG) and ShinyGO v0.77 and Enrichr for pathway enrichment analysis. Results: The overexpression of CST1 resulted in a total of 23 DEG (3 upregulated and 20 downregulated) and the overexpression of CCL26 in a total of 113 DEG (3 upregulated and 110 downregulated). The gene ontology enrichment analysis showed a significant downregulation of type I and III interferon signaling pathway genes as well as interferon-stimulated genes. Conclusion: Our results indicate that an overexpression of CST1 and especially CCL26 cause a downregulation of interferon related genes. It might cause a higher disease susceptibility, mainly for allergic asthma, as CCL26 is an agonist for CCR-3-carrying cells, such as eosinophils and Th2 lymphocytes, mostly active in allergic asthma. Comparative gene expression profiling analysis of RNA-seq data from A549 cells transfected with plasmids containing the human CST1 and CCL26 as well as the empty vector pCMV6-entry as control