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

  1. Author:
    Yazar, Volkan
    Yilmaz, Ismail Cem
    Bulbul, Artun
    Klinman, Dennis M
    Gursel, Ihsan

  2. Author Address

    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Thorlab, Molecular Biology and Genetics Department, Faculty of Science, Ihsan Dogramaci Bilkent University, 06800 Ankara, Turkey., Izmir Biomedicine and Genome Center, Dokuz Eylul University, Balcova, Izmir, Turkey., Immune Modulation Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.,
    1. Year: 2023
    2. Date: Mar 14
    3. Epub Date: 2023 02 04
  2. Journal: Molecular Therapy. Nucleic Acids
    1. 31
    2. Pages: 553-565
  4. Type of Article: Article
  1. Abstract:

    Homeostatic 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. © 2023 The Author(s).

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External Sources

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  2. DOI: 10.1016/j.omtn.2023.02.004
  3. PMID: 36895952
  4. PMCID: PMC9989320
  5. PII : S2162-2531(23)00024-0

Library Notes

  1. Fiscal Year: FY2022-2023
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