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Gene expression profile of microglia following traumatic brain injury and adoptive transfer of Tregs at acute and chronic timepoints

ABSTRACT: To investigate whether the immunomodulatory effects of nasal anti-CD3 on the microglial transcriptomic profile following TBI is dependent on Tregs, we employed adoptive transfer experiments

ORGANISM(S): Mus musculus

PROVIDER: GSE276649 | GEO | 2025/01/15

REPOSITORIES: GEO

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Gene expression profile of microglia following traumatic brain injury and nasal anti-CD3 treatment at acute and chronic timepoints

Project description:Bulk RNA-sequencing was performed to characterize the gene expression profile of microglia at acute and chronic timepoints following traumatic brain injury and nasal anti-CD3 treatment. We further investigated how the chronic microglial transcriptomic profile is modulated following traumatic brain injury and nasal anti-CD3 treatment in female mice with severe TBI, and in male mice with a delayed administration of treatment post-injury.

2025-01-15 | GSE276647 | GEO

Transcriptomic profiling of brain-infiltrating and peripheral CD4+Foxp3+ Tregs following traumatic brain injury and nasal anti-CD3 treatment

Project description:We performed bulk RNA-sequencing analysis of brain and blood CD4+Foxp3+ Treg cells from sham and injured mice to characterize the gene expression profile of Tregs following traumatic brain injury and nasal anti-CD3 treatment

2025-01-15 | GSE276646 | GEO

Gene expression profile of phagocytic and non-phagocytic microglia following traumatic brain injury and nasal anti-CD3 treatment

Project description:Bulk RNA-sequencing was performed to investigate the transcriptomic signature of phagocytic and non-phagocytic microglia following traumatic brain injury and nasal anti-CD3 treatment.

2025-01-15 | GSE276739 | GEO

Effect of blocking the IL-10 receptor on the microglial transcriptomic signature following chronic traumatic brain injury and nasal anti-CD3 treatment

Project description:Investigating the impact of blocking the IL-10 receptor on the gene expression profile of microglia following chronic traumatic brain injury and nasal anti-CD3 treatment.

2025-01-15 | GSE276648 | GEO

Transcriptome profiling in the DA and PVG inbred rat strains after traumatic brain injury

Project description:Genetic factors are believed to be of importance for outcome of traumatic brain injury (TBI). However, so far mainly allelic variation in apolipoprotein E4 has been studied in human TBI. In order to study the role of genetic factors in experimental TBI, we examined parental DA and PVG strains before and after TBI. A standardized weight drop injury was used and the pericontusional area was dissected 1 day after TBI and transcriptional profiling was performed.

2012-09-06 | E-MTAB-795 | biostudies-arrayexpress

Screening for altered plasma miRNAs in traumatic brain injured patients

Project description:In this study, we examined if the composition of plasma miRNAs is altered in patients with traumatic brain injury (TBI), and if these changes can be used as diagnostic markers. A microarray containing 875 human miRNAs was used to compare the miRNA profile of plasma collected from severe TBI patients (GCS M-bM-^IM-$ 8) to that of age-, gender-, and race-matched healthy volunteers. This screen identified 108 miRNAs in the plasma of healthy volunteers. Of these, 52 were found to be altered in plasma samples from persons with severe TBI, and an additional 8 miRNAs were detected only in the plasma of TBI patients. Plasma samples from 10 patients from either severe TBI (experimental group) or healthy volunteers (reference group; age-, gender-, and race-matched ) were pooled, the total RNA extracted in parallel, eluted in 100ul, and dried to 30 ul. Equal volumes of extracted plasma RNAs were assayed for global miRNA content using a service provider (LC Sciences, Houston, TX). There were no replicates performed for this screen. Healthy volunteer group served as the reference.

2011-04-06 | E-GEOD-21854 | biostudies-arrayexpress

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy.

Project description:Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR). Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

| S-EPMC5363324 | biostudies-literature

Cerebral hypoperfusion exacerbates traumatic brain injury in male mice

Project description:Traumatic brain injury (TBI) has been postulated to initiate a disease process that interacts with vascular dysfunction. However, the combined effects of preexisting cerebral hypoperfusion and TBI remain poorly explored. This study aimed to investigate the combined effects of bilateral carotid artery stenosis (BCAS) and mild-moderate TBI on cerebral blood flow (CBF), cognitive function, histology, and transcriptomics in Swiss-Webster mice. Male and female mice underwent BCAS using steel microcoils around the carotid arteries, followed by TBI 30 days post coil implantation. CBF, spatial learning and memory, axonal damage, and gene expression profiles were assessed. BCAS led to a ~10% reduction in CBF, while TBI caused a similar decrease. However, mice exposed to both BCAS and TBI exhibited more pronounced reductions in CBF, associated with marked spatial learning and memory deficits, particularly in males. Axonal damage in male mice was also exacerbated by the combination of BCAS and TBI. Notably, females demonstrated differential vascular and cognitive responses to BCAS and TBI, suggesting sex-specific protective mechanisms. Single nuclei RNA sequencing revealed unique, cell type-specific gene expression alterations due to BCAS, TBI, or the combination. Moreover, BCAS and TBI induced significant gene expression changes in various cell types, hinting at complex cellular interactions following vascular challenges and trauma. The cellular and molecular interplay between hypoperfusion and TBI points to intricate vascular-neuronal interactions and potential avenues for targeted interventions.

2024-08-14 | GSE241690 | GEO

Microarray analysis of brain macrophage subsets and peripheral blood monocytes in traumatic brain injury

Project description:We compared arginase-1+ macrophages (macrophages were defined by flow cytometry as CD45hi CD11b+ Ly6G-) with arginase-1- brain macrophages following traumatic brain injury (TBI) by isolating these cells from YARG transgenic mice, which express YFP under the arginase-1 promoter. Both cell populations were isolated from YARG brain tissues one day following TBI. We also examined the expression profile of peripheral blood monocytes (monocytes were defined by flow cytometry as CD11bhi F4/80+) from injured YARG mice and from normal YARG mice. Peripheral blood samples were compared to TBI brain macrophages to assess gene expression changes before and after infiltration into the brain. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an IRES inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21Â±1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by YFP. Gene expression analysis of Arg1+ and Arg1- brain macrophage populations revealed that these populations were distinct from either classically activated (M1) macrophages or M2 macrophages, with features of both. The Arg1+ cells differed from Arg1- cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI involves recruitment of at least two major macrophage subsets. Overall, our data indicate that the macrophage response to TBI is heterogeneous and unique. Four groups (Arg1- brain macrophages post-TBI, Arg1+ brain macrophages post-TBI, normal blood monocytes, blood monocytes post-TBI) were analyzed. Four replicates of each group were analyzed for a total of 16 samples (only 3 replicates of the blood monocyte groups are included in this submission).

2013-05-01 | E-GEOD-39759 | biostudies-arrayexpress

Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy

Project description:Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) -retroviral vectors. Analysis of clinical transgenic adoptive cell therapy products in vivo revealed that despite strong persistence of the transgenic TCR DNA sequence over time, its expression was profoundly decreased over time at the RNA and protein levels. Patients with the greatest degrees of expression suppression displayed significant increases in DNA methylation over time within the MSCV promoter region, as well as progressive increases in DNA methylation within the entire MSCV vector over time. These increases in vector methylation occurred independently of its integration site within the host genomes. These results have significant implications for the design of future viral-vector gene engineered adoptive cell transfer therapies.

2020-07-06 | GSE153820 | GEO

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