Gene network landscape of murine splenocytes reveals integrin as the A151 ODN-responsive hub in immune transcriptome
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PROVIDER: PRJNA767337 | ENA |
REPOSITORIES: ENA
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Project description:PURPOSE: 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 immune response by a subset of white corpuscles through repetitive telomere derived TTAGGG sequences. Nevertheless, the genuine effect A151 has on immune cell transcriptome still remains unknown. METHODS: We leveraged an integrative approach in which weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis of our in-house microarray data sets aided our understanding of how A151 ODN suppresses immune response in mouse splenocytes. We fed raw gene expression data from two different (scrambled ODN and A151 ODN) treatment groups with a varying number of replicate arrays (29 and 16, respectively) into WGCNA, limma, and GSEA separetely to understand different dimensions of the A151 ODN-driven immune modulation at the transcriptome level. RESULTS: Together with experimental and in silico validations, we demonstrated that A151 ODN acts on components of integrin complexes, namely Itgam and Itga6, to interfere with immune cell adhesion, and thereby, suppress the immune response in mouse. Furthermore, we revealed that cell adhesion by integrin complexes serves as a focal point for cellular response to A151 ODN treatment in immune cells. CONCLUSION: A refined set of co-hub genes led by Itgam and Itga6 plays a pivotal role in A151 ODN-driven suppression of immune response. Also, A151 ODN treatment appears to interfere with immune cell adhesion to quench immune response in mouse splenocytes. The outcome of this study sheds light on the molecular basis of immune suppression by a clinically useful DNA-based therapeutic agent and may open new revenues for A151 ODN research.
2021-10-01 | GSE184994 | GEO
Project description: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.
| S-EPMC9989320 | biostudies-literature
Project description:CpG-ODN is a potent immuno-stimulatory molecule. In order to exclude a direct effect of murine CpG-ODN on IGROV1 human ovarian cancer cell line a gene expression experiment was performed.
2011-04-01 | GSE23442 | GEO
Project description:A subset of T-ALL/T-LBL patients is characterized by overexpression of the oncogenic Serine/Threonine kinase PIM1. Mechanisms for PIM1 overexpression are translocations involving the TCRb and PIM1 loci, JAK/STAT activating mutations and responsiveness to cytokinens in the tumor microenvironment, such as IL7. In this study, we generated a TLX3+ JAKwt/STATwt IL7 responsive T-ALL PDX model using NSG mice. Splenocytes were ex vivo treated with the PIM inhibitor PIM447 and QuantSeq 3’ mRNA sequencing was performed, in order to elucidate the transcriptional effects and molecular mechanisms by which PIM447 induces apoptosis in T-ALL PDX cells.
2020-02-17 | GSE145165 | GEO
Project description:CD14+ purified bovine monoctye stimulation with CpG ODN 2007 vs. GpC ODN 2007, CpG 2007 vs. Control, GpC 2007 vs. Control and Media vs Control (Control is unstimluated CD14+ purified bovine monocytes at time zero). Before stimulation, the CD14+ purified bovine monocytes were rested for 20 h. Then the cells were stimulated for 4hrs.
2005-01-01 | E-FPMI-2 | biostudies-arrayexpress
Project description:To explore TNF-related genes in GPI-induced arthritis, we performed GeneChip analysis using arthritic splenocytes and control-immunized splenocytes. Among the arrayed TNFalpha-related genes, TIARP mRNA was highly expressed in arthritic splenocytes, with levels exceeding more than 20-times the control splenocytes
2009-07-24 | GSE17272 | GEO
Project description:This study aims at identifying a dual transcriptomics and metabolomics blood signature following administration of CpG-ODN (cytosine-phosphate-guanine oligodeoxynucleotides), a reference immune-stimulatory molecule. A clinical study was conducted with chicks and transcriptomics and metabolomics analyses were performed on whole-blood and plasma samples respectively. Statistical analyses resulting in lists of differentially expressed genes and metabolites with different abundance were identified in chicks treated with CpG-ODN. The results showed that CpG-ODN activates the innate immune systems within hours following administration and its effect lasts over time, as metabolomic and transcriptomic profiles are still varying at 6 days after administration.
2019-10-17 | GSE138956 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE23440: Gene expression profiling of IGROV1 cells after in vitro treatment with ascitic fluid from human ovarian cancer bearing mice GSE23441: IGROV1 gene expression analysis after in vivo locoregional treatment with CpG-ODN GSE23442: Gene expression profile of IGROV1 cells after in vitro treatment with CpG-ODN Refer to individual Series
2011-04-01 | E-GEOD-23491 | biostudies-arrayexpress
Project description:Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. We used microarrays to detail the global program of gene expression underlying the sepsis-induced changes in CD4+ splenocyte phenotype. Keywords: disease state analysis
2006-06-01 | GSE4479 | GEO
Project description:CpG-ODN is a potent immuno-stimulatory molecule. In order to exclude a direct effect of murine CpG-ODN on IGROV1 human ovarian cancer cell line a gene expression experiment was performed. The ovarian cancer cell line IGROV-1 was obtained from the ATCC (Rockville, MD). Cells were routinely maintained in RPMI medium 1640 (Sigma, St. Louis, MO) supplemented with 10% FCS (Sigma) and 2 mM glutamine (Cambrex, East Rutherford, NJ). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 1x106 IGROV-1 cells were seeded in 6-well plates and, after seeding, cells were treated with 10uM of CpG-ODN in culture medium [phosphorothioated ODN1826 (5’-TCCATGACGTTCCTGACGTT-3’), TriLink Biotechnologies (San Diego, CA, USA)] for 24 hours. At the end of treatment, cells were collected and RNA extracted.
2011-04-01 | E-GEOD-23442 | biostudies-arrayexpress