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The functional role of CST1 and CCL26 in asthma development

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Title: The functional role of CST1 and CCL26 in asthma development
Authors: Hoyer, Angela, Chakraborty, Sandip, Lilienthal, Ingrid, Konradsen, Jon R., Katayama, Shintaro, Söderhäll, Cilla
Contributors: Research Programs Unit, STEMM - Stem Cells and Metabolism Research Program
Publisher Information: John Wiley & Sons Ltd.
Publication Year: 2024
Collection: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
Subject Terms: A549, Ccl26, Cst1, Olink, RNA sequencing, Allergic asthma, General medicine, internal medicine and other clinical medicine
Description: BackgroundAsthma 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.MethodsA549 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, |log2FC | >= 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 |log2FC| >= 1, p < .05.ResultsThe 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.ConclusionOur 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. ; Peer reviewed
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: The authors acknowledge the support from the National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. Support by NBIS (National Bioinformatics Infrastructure Sweden) is gratefully acknowledged. The authors would also like to thank the Affinity Proteomics-Stockholm Facility at SciLifeLab for conducting the Olink proximity extension assay analyses.; Hoyer , A , Chakraborty , S , Lilienthal , I , Konradsen , J R , Katayama , S & Söderhäll , C 2024 , ' The functional role of CST1 and CCL26 in asthma development ' , Immunity, Inflammation and Disease , vol. 12 , no. 1 , e1162 . https://doi.org/10.1002/iid3.1162; http://hdl.handle.net/10138/570773; 85182678301; 001145553600001
Availability: http://hdl.handle.net/10138/570773
Rights: cc_by ; info:eu-repo/semantics/openAccess ; openAccess
Accession Number: edsbas.5B0231F6
Database: BASE
Description
Abstract:BackgroundAsthma 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.MethodsA549 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, |log2FC | >= 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 |log2FC| >= 1, p < .05.ResultsThe 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.ConclusionOur 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. ; Peer reviewed