RNA-Seq of CD3+ T cells flow sorted from MLR assays with TNF/TNFR inhibitory compound combination treatments
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE339038 | GEO | 2026/07/17
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Ozone (O3) is the predominant oxidant air pollutant associated with respiratory inflammation, lung dysfunction, and worsening preexisting airway diseases. We determined that TNFR signlaing pathway plays a key role in lung injury and inflammation caused by O3 in mice. However, downstream molecular mechanisms underlying TNFR pathway have not been investigated. Methods: To investigate the role of TNFR pathway in gene expression changes, Tnfr1/2-deficient (Tnfr-/-) and wild-type (Tnfr+/+, C57BL/6J) mice were exposed to air or 0.3-ppm O3. Total RNAs were isolated from lung homogenates and cDNA microarray analyses were performed to elucidate TNFR-directed transcriptomics in basal lungs (air-exposed) as well as in the lung exposed to time course of O3 (24, 48, and 72 hr). Results: O3 caused time-dependent changes in lung gene expressions with the greatest transcriptome changes at 48-72 hr of exposure in Tnfr+/+ mice. At early time of exposure (24 hr), acute phase and inflammatory responses gene as well as redox and lipid metabolism genes were increased by O3 while cell cycle and DNA damage repair genes were markedly increased by O3 at later time points (48-72 hr). Compared to Tnfr+/+ mice, Tnfr-/- mice had lowered expression of inflammatory response and vascular disorder-related genes at baseline (air). After O3 exposure, Tnfr-/- had enhanced expression of immune and inflammatory genes at 24 hr, indicating compensatory or adpative poentiation of immunity in Tnfr-/- mice. At 48 hr of O3 exposure, Tnfr-/- mice showed suppressed expression of genes involved in epithelial proliferation, inflammatory cell influxes and epithelial injury, compared to Tnfr+/+ mice. At 72 hr of O3 exposure, neurodegeneration and neurotransmitter transport genes were suppressed in Tnfr-/- than in Tnfr+/+. Conclusion: Overall, deficiency of TNFR-mediated signaling in mouse lungs altered transcriptomes to protect lungs from O3-induced inflammation, cell proliferation, oxidative stress, and neuronal disorders.
2021-09-29 | GSE166399 | GEO
Project description:The Mixed Lymphocyte Reaction (MLR) consists in the allogenic co-culture of monocytes derived dendritic cells (MoDCs) with T cells from another donor. This in vitro assay is largely used for the assessment of immunotherapy compounds. Nevertheless, the phenotypic changes associated with lymphocyte responsiveness under MLR have never been thoroughly evaluated. Here, we used multiplex cytokine and chemokine assays, multiparametric flow cytometry and single cell RNA-sequencing to deeply characterize T cells activation and function in the context of CD4+- and CD8+-specific MLR kinetics. We showed that CD4+ and CD8+ T cells in MLR share common classical markers of response such as polyfunctionality, increased proliferation and CD25 expression but differ in their kinetics and amplitude of activation as well as their patterns of cytokines secretion and immune checkpoints expression. The analysis of immunoreactive KI67+CD25+ T cells identified PBK, LRR1 and MYO1G as new potential biomarkers of MLR response. Using cell-cell communication network inference and pathway analysis on single cell RNA-sequencing data, we also highlighted key components of the immunological synapse occurring between T cells and the stimulatory MoDCs together with downstream signaling pathways involved in CD4+ and CD8+ T cells activation. These results provide a deep understanding of the kinetics of the MLR assay for CD4+ or CD8+ T cells and may allow to identify new strategies for immunotherapy in cancer.
2024-01-05 | GSE242428 | GEO
Project description:To understand how the combination of ORIN1001 plus docetaxel promotes anti-tumor immunity, we performed single-cell RNA sequencing (scRNA-seq) of CD45+ cells from 2153L tumors. Our data found that combo induces CD8+ T cells that express high levels of T cell activation, cytotoxicity, and exhaustion genes. combo also increase the cDC1 and MHC-II high macrophages which exhibited higher M1-like macrophages scores.
2024-10-16 | GSE276356 | GEO
Project description:RNPS1 inhibits excessive TNF/TNFR signaling to support hematopoiesis in mice
| PRJNA649939 | ENA
Project description:Tumor microenvironment with distinctive cell types and a complex extracellular matrix has a tremendous effect on cancer progression. In the present study we investigated the effects of proinflammatory (M1) and immunosuppressive (M2) macrophages on melanoma cell hyaluronan (HA) metabolism and inflammatory response. M1 macrophages stimulated the formation of a thick pericellular HA matrix in melanoma cells, and the overall HA synthesis was increased due to upregulation of HA synthases (HAS) 1 and 2. HAS2 silencing reversed the effect of M1 CM (conditioned medium) on pericellular HA coat formation, similarly as the chemical inhibitors for TNFR (R-7050), IKK2 (IKK16) and MEK (U0126). RNA sequencing analysis indicated that several inflammation related genes (IL1, IL6, CXCL6) were highly upregulated in M1 CM treated melanoma cells. Gene set enrichment analysis identified that genes related to inflammatory response and TNFα signaling via NF-κB are enriched in M1 CM treated cells. Our results indicate that the activation of MEK and TNFR-NF-κB signaling leads to HAS2 upregulation, while MEK signaling pathway is not involved in cytokine upregulation. Furthermore, HAS2 silencing downmodulated the M1 CM-induced cytokine expression. Our results indicate that proinflammatory macrophages induce an inflammatory response in melanoma cells, where HAS2 upregulation associates with a protumor inflammatory gene signature.
2022-04-26 | GSE178744 | GEO
Project description:M1 macrophages induce an inflammatory phenotype in melanoma cells via TNFR-NF-κB signaling
| PRJNA740275 | ENA
Project description:Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections.
2016-03-07 | GSE17946 | GEO
Project description:Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections.
2016-03-07 | GSE17606 | GEO
Project description:Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections. CD4+ T cells from Infliximab or control treatment of chronic LCMV infected animals
2016-03-07 | GSE52184 | GEO
Project description:Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections. TNF stimulation of CD4+ T cells to generate a CD4+ T-cell specific RNA-fingerprint
2016-03-07 | GSE52182 | GEO