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...

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Autores principales:	Amanda Hazy, Lauren Bochicchio, Andrea Oliver, Eric Xie, Shuo Geng, Thomas Brickler, Hehuang Xie, Liwu Li, Irving C. Allen, Michelle H. Theus
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2112364c5c2c46e18080b771e9c331dc
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spelling	oai:doaj.org-article:2112364c5c2c46e18080b771e9c331dc2021-12-02T15:09:38ZDivergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury10.1038/s41598-019-45089-z2045-2322https://doaj.org/article/2112364c5c2c46e18080b771e9c331dc2019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45089-zhttps://doaj.org/toc/2045-2322Abstract 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.Amanda HazyLauren BochicchioAndrea OliverEric XieShuo GengThomas BricklerHehuang XieLiwu LiIrving C. AllenMichelle H. TheusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/2112364c5c2c46e18080b771e9c331dc
work_keys_str_mv	AT amandahazy divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT laurenbochicchio divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT andreaoliver divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT ericxie divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT shuogeng divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT thomasbrickler divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT hehuangxie divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT liwuli divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT irvingcallen divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury AT michellehtheus divergentagedependentperipheralimmunetranscriptomicprofilefollowingtraumaticbraininjury
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Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury

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