Gene network landscape of mouse splenocytes reveals integrin complex as the A151 ODN-responsive hub molecule in the immune transcriptome

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buir.contributor.authorYazar, Volkan
buir.contributor.authorYılmaz, İsmail Cem
buir.contributor.authorBülbül, Artun
buir.contributor.authorGürsel, İhsan
dc.citation.epage565en_US
dc.citation.spage553
dc.citation.volumeNumber31
dc.contributor.authorYazar, Volkan
dc.contributor.authorYılmaz, İsmail Cem
dc.contributor.authorBülbül, Artun
dc.contributor.authorKlinman, D. M.
dc.contributor.authorGürsel, İhsan
dc.date.accessioned2024-03-17T12:18:57Z
dc.date.available2024-03-17T12:18:57Z
dc.date.issued2023-02-01
dc.departmentDepartment of Molecular Biology and Genetics
dc.description.abstractHomeostatic restoration of an inflammatory response requires quenching of the immune system after pathogen threats vanish. A continued assault orchestrated by host defense results in tissue destruction or autoimmunity. A151 is the epitome of synthetic oligodeoxynucleotides (ODNs) that curb the immune response by a subset of white corpuscles through repetitive telomere-derived TTAGGG sequences. Currently, the genuine effect of A151 on the immune cell transcriptome remains unknown. Here, we leveraged an integrative approach where weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and gene set enrichment analysis (GSEA) of our in-house microarray datasets aided our understanding of how A151 ODN suppresses the immune response in mouse splenocytes. Our bioinformatics results, together with experimental validations, indicated that A151 ODN acts on components of integrin complexes, Itgam and Itga6, to interfere with immune cell adhesion and thereby suppresses the immune response in mice. Moreover, independent lines of evidence in this work converged on the observation that cell adhesion by integrin complexes serves as a focal point for cellular response to A151 ODN treatment in immune cells. Taken together, the outcome of this study sheds light on the molecular basis of immune suppression by a clinically useful DNA-based therapeutic agent.
dc.description.provenanceMade available in DSpace on 2024-03-17T12:18:57Z (GMT). No. of bitstreams: 1 Gene_network_landscape_of_mouse_splenocytes_reveals_integrin_complex_as_the_A151_ODN-responsive_hub_molecule_in_the_immune_transcriptome.pdf: 7552939 bytes, checksum: 0fc7db7e9f4dca3a7c244058ec182f89 (MD5) Previous issue date: 2023-02-01en
dc.identifier.doi10.1016/j.omtn.2023.02.004
dc.identifier.eissn2162-2531
dc.identifier.urihttps://hdl.handle.net/11693/114843
dc.publisherCell Press
dc.relation.isversionofhttps://dx.doi.org/10.1016/j.omtn.2023.02.004
dc.rightsCC BY-NC-ND 4.0 DEED (Attribution-NonCommercial-NoDerivs 4.0 International)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.source.titleMolecular Therapy Nucleic Acids
dc.titleGene network landscape of mouse splenocytes reveals integrin complex as the A151 ODN-responsive hub molecule in the immune transcriptome
dc.typeArticle

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