{Reference Type}: Journal Article
{Title}: The functional role of CST1 and CCL26 in asthma development.
{Author}: Hoyer A;Chakraborty S;Lilienthal I;Konradsen JR;Katayama S;Söderhäll C;
{Journal}: Immun Inflamm Dis
{Volume}: 12
{Issue}: 1
{Year}: 2024 Jan
{Factor}: 2.493
{DOI}: 10.1002/iid3.1162
{Abstract}: <B>BACKGROUND: </B>Asthma is the most common chronic disease in children with an increasing prevalence. Its development is caused by 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) in nasal epithelium. The aim of our study was to investigate the functional mechanism of CST1 and CCL26 in the alveolar basal epithelial cell line A549.<BR><B>METHODS: </B>A549 cells were transfected with individual overexpression vectors for CST1 and CCL26 and RNA sequencing was performed to examine the transcriptomics. edgeR was used to identify differentially expressed genes (= DEG, |log2 FC | ≥ 2, FDR < 0.01). The protein expression levels of A549 cells overexpressing CST1 and CCL26 were analyzed using the Target 96 inflammation panel from OLINK (antibody-mediated proximity extension-based assay; OLINK Proteomics). Differentially expressed proteins were considered with a |log2 FC| ≥ 1, p < .05.<BR><B>RESULTS: </B>The overexpression of CST1 resulted in a total of 27 DEG (1 upregulated and 26 downregulated) and the overexpression of CCL26 in a total of 137 DEG (0 upregulated and 137 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. At the protein level, overexpression of CST1 induced a significantly increased expression of CCL3, whereas CCL26 overexpression led to increased expression of HGF, and a decrease of CXCL11, CCL20, CCL3 and CXCL10.<BR><B>CONCLUSIONS: </B>Our results indicate that an overexpression of CST1 and CCL26 cause a downregulation of interferon related genes and inflammatory proteins. 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.