Interferon Signaling After TBI in Aged Mice
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ABSTRACT:
PROVIDER: PRJNA749604 | ENA |
REPOSITORIES: ENA
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Project description:Type I Interferons (IFN-I) contribute to the neuropathology of traumatic brain injury (TBI) and age-related neurodegenerative disease, where Cyclic GMP-AMP Synthase (cGAS) and the Stimulator of Interferon Genes (STING) pathway are implicated as key inducers of IFN-I responses. This study evaluated cGAS/STING activation, IFN-I signaling and neuroinflammation in the cortex and hippocampus of young and aged C57Bl/6 male mice, 24 hrs after controlled cortical impact injury. TBI increased expression of transcripts related to IFN-I signaling and activation of cGAS in the injured cortex of aged mice compared to younger mice. These observations were confirmed by RT-PCR, western blotting and phosphorylation/activation of STAT1, a downstream IFN-I effector molecule
2021-08-20 | GSE180811 | GEO
Project description:Using 10x Genomics' single-cell RNA-seq (scRNA-seq) technology, we profiled expression of genes in cell type-specific MAGL knockout mice that received TBI. We found that there are differences in expression of genes between WT, tKO, nKO, and aKO mice in sham or TBI.
2021-06-22 | GSE178226 | GEO
Project description:Patients aged 65 years and older account for an increasing proportion of those who suffer from traumatic brain injury (TBI). Aged TBI patients experience increased morbidity and mortality compared to young TBI patients. Our prior data demonstrated that anti-CD49d antibody (aCD49d Ab), an FDA-approved drug that blocks α4 integrin, abrogates infiltration of CD8+ T-cells into the injured brain, improves survival, and attenuates neurocognitive deficits. Yet, the molecular mechanisms underlying the therapeutic effects of aCD49d Ab remained unexplored. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, we found that mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of CD8+ T cell cytotoxicity. Further, aCD49d Ab further produces a neuroprotective Th2 response and restores age-associated CD8+ T cell senescence. Our results demonstrate that targeting infiltrating CD8+ T cells with aCD49d Ab is a promising therapeutic strategy for treating TBI in aged individuals.
2024-10-23 | GSE260719 | GEO
Project description:Tissue damage precedes GvHD and the events leading up to this inflammatory disease are not well understood. To identify cell populations that may invade the intestinal tract after total body irradiation (TBI), we performed a microarray based gene expression analysis of the intestinal tract isolated from untreated mice or mice that had received 9 Gray TBI 24 h or 48 h previously. The aim of the microarray based gene expression analysis was to identify genes specific for certain cell populations that may contribute to GvHD.
2014-04-28 | E-MTAB-1566 | biostudies-arrayexpress
Project description:PR attentuation of interferon signaling
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Project description:Traumatic brain injury (TBI) induces neuroinflammatory innate immune responses that plays roles in both worsening brain damage and facilitating functional recovery. A major goal is to understand the heterogeneity of the immune responses to TBI, and to precisely identify key components that impact functional outcomes. We previously demonstrated that genetically targeting Ccr2 in a mouse model of controlled cortical impact led to neuroprotection in TBI. Our current studies of TBI use single cell RNA sequencing of over 10,000 TBI ipsilateral brain leukocytes to examine the mechanisms associated with the observed benefit in Ccr2-/- mice by comparing gene expression in leukocyte subsets from Ccr2-/- mice to gene expression in C57BL/6 wild type mice. Unbiased clustering identified two monocyte subsets, Chil3hi Ly6Chi classical monocytes and Gpnmbhi Ly6Clo nonclassical monocytes, and nine microglia states in the ipsilateral TBI brain. Comparative analysis between the genotypes revealed that Ccr2-/- TBI mice contained reduced numbers of inflammatory macrophages. In TBI, we observed a subset of microglia highly expressing several type I interferon-stimulated genes (ISGs) and is designated as Irf7hi microglia. Notably, unbiased differential expression analysis detected a two-fold reduction in the type I interferon response in multiple Ccr2-/- TBI microglia subsets compared to wild type TBI microglia. Treatment post-injury with a human CCR2 (hCCR2) inhibitor, CCX872, in hCcr2 knock-in mice improved cognitive function post-TBI, and also correlated with reduced expression of a key ISG, Irf7. We identified and characterized macrophage and microglia subsets during acute TBI. Our data showed that a reduction in macrophage expansion in TBI by both genetic and pharmacological methods, improved TBI and correlated with a reduction in the type I IFN response. These data indicate that macrophage expansion co-directs a type IFN response in microglia, and that targeting macrophage expansion in the brain can alter the profile of microglia subsets and lead towards improved functional outcomes.
2019-04-18 | GSE129927 | GEO
Project description:Comparison of post-injury (sham versus severe TBI) gene expression changes using a Drosophila head-specific TBI model.
2021-07-20 | GSE171185 | GEO
Project description:LNK suppresses interferon signaling in melanoma
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Project description:Skeletal muscle of aged mice, and aged treated with myriocin
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Project description:Single-cell RNA-seq analysis in TBI mgll KO mice
| PRJNA737768 | ENA