Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury
Abstract The peripheral immune system is a major regulator of the pathophysiology associated with traumatic brain injury (TBI). While age-at-injury influences recovery from TBI, the differential effects on the peripheral immune response remain unknown. Here, we investigated the effects of TBI on gen...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2019-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-45089-z |
| _version_ | 1818997831221903360 |
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| author | Amanda Hazy Lauren Bochicchio Andrea Oliver Eric Xie Shuo Geng Thomas Brickler Hehuang Xie Liwu Li Irving C. Allen Michelle H. Theus |
| author_facet | Amanda Hazy Lauren Bochicchio Andrea Oliver Eric Xie Shuo Geng Thomas Brickler Hehuang Xie Liwu Li Irving C. Allen Michelle H. Theus |
| author_sort | Amanda Hazy |
| collection | DOAJ |
| description | Abstract The peripheral immune system is a major regulator of the pathophysiology associated with traumatic brain injury (TBI). While age-at-injury influences recovery from TBI, the differential effects on the peripheral immune response remain unknown. Here, we investigated the effects of TBI on gene expression changes in murine whole blood using RNAseq analysis, gene ontology and network topology-based key driver analysis. Genome-wide comparison of CCI-injured peripheral whole blood showed a significant increase in genes involved in proteolysis and oxidative-reduction processes in juvenile compared to adult. Conversely, a greater number of genes, involved in migration, cytokine-mediated signaling and adhesion, were found reduced in CCI-injured juvenile compared to CCI-injured adult immune cells. Key driver analysis also identified G-protein coupled and novel pattern recognition receptor (PRR), P2RY10, as a central regulator of these genes. Lastly, we found Dectin-1, a c-type lectin PRR to be reduced at the protein level in both naïve neutrophils and on infiltrating immune cells in the CCI-injured juvenile cortex. These findings demonstrate a distinct peripheral inflammatory profile in juvenile mice, which may impact the injury and repair response to brain trauma. |
| first_indexed | 2024-12-20T21:51:53Z |
| format | Article |
| id | doaj.art-2112364c5c2c46e18080b771e9c331dc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:51:53Z |
| publishDate | 2019-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2112364c5c2c46e18080b771e9c331dc2022-12-21T19:25:32ZengNature PortfolioScientific Reports2045-23222019-06-01911910.1038/s41598-019-45089-zDivergent age-dependent peripheral immune transcriptomic profile following traumatic brain injuryAmanda Hazy0Lauren Bochicchio1Andrea Oliver2Eric Xie3Shuo Geng4Thomas Brickler5Hehuang Xie6Liwu Li7Irving C. Allen8Michelle H. Theus9The Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Statistics, Virginia TechThe Department of Biological Sciences, College of Science, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Biological Sciences, College of Science, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechThe Department of Biomedical Sciences and Pathobiology, Virginia TechAbstract The peripheral immune system is a major regulator of the pathophysiology associated with traumatic brain injury (TBI). While age-at-injury influences recovery from TBI, the differential effects on the peripheral immune response remain unknown. Here, we investigated the effects of TBI on gene expression changes in murine whole blood using RNAseq analysis, gene ontology and network topology-based key driver analysis. Genome-wide comparison of CCI-injured peripheral whole blood showed a significant increase in genes involved in proteolysis and oxidative-reduction processes in juvenile compared to adult. Conversely, a greater number of genes, involved in migration, cytokine-mediated signaling and adhesion, were found reduced in CCI-injured juvenile compared to CCI-injured adult immune cells. Key driver analysis also identified G-protein coupled and novel pattern recognition receptor (PRR), P2RY10, as a central regulator of these genes. Lastly, we found Dectin-1, a c-type lectin PRR to be reduced at the protein level in both naïve neutrophils and on infiltrating immune cells in the CCI-injured juvenile cortex. These findings demonstrate a distinct peripheral inflammatory profile in juvenile mice, which may impact the injury and repair response to brain trauma.https://doi.org/10.1038/s41598-019-45089-z |
| spellingShingle | Amanda Hazy Lauren Bochicchio Andrea Oliver Eric Xie Shuo Geng Thomas Brickler Hehuang Xie Liwu Li Irving C. Allen Michelle H. Theus Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury Scientific Reports |
| title | Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury |
| title_full | Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury |
| title_fullStr | Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury |
| title_full_unstemmed | Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury |
| title_short | Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury |
| title_sort | divergent age dependent peripheral immune transcriptomic profile following traumatic brain injury |
| url | https://doi.org/10.1038/s41598-019-45089-z |
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