Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297041 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor-Host Signaling Interaction Reveals a Systemic, Age-Dependent Splenic Immune Influence on Tumor Development
| PRJNA297040 | ENA
Project description:Tumor-Host Signaling Interaction Reveals a Systemic, Age-Dependent Splenic Immune Influence on Tumor Development [LLC tumor bearing mice]
| PRJNA297042 | ENA
Project description:The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
2015-10-12 | GSE73450 | GEO
Project description:The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
2015-10-12 | GSE73449 | GEO
Project description:Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to “hallmark” processes impacting tumor development, in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally, protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74, and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation, operative through host age, that would indicate a modulation of host’s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression, carcinogenesis, and genetic perturbation by old age.
2015-06-22 | GSE67243 | GEO
Project description:The functional integration of innate immune and metabolic signaling responses represents an ancient strategy to manage infections in metazoans. Using Drosophila, we uncovered that immune-metabolic sensing in muscle dictates resistance to enteric bacterial infection through vitamins dependent metabolic remodeling. Within muscle, the activation strength of systemic innate immune signaling, integrated with mitochondrial-dependent glutamate dehydrogenase (Gdh) function, conditions lipid mobilization from adipose. Mild intramuscular IMD/innate immune signaling activity allows for infection-mediated increases in mitochondrial biogenesis/function, which further stimulates mitochondria/Gdh-dependent synthesis of glutamate. Intramuscular derived glutamate acts as a systemic metabolite to influence lipid mobilization through altering vitamin metabolism. This lipid mobilization improves bacterial clearance and boost infection resistance. Conversely, elevated activation of IMD/innate immune signaling in muscle impedes infection-mediated increases in mitochondrial biogenesis/function and subsequent metabolic remodeling. Finally, life history traits that fine-tune intramuscular mitochondrial dynamics consequently influence infection resistance and shape phenotypic diversity of infection responses within populations.
2021-11-19 | GSE160652 | GEO
Project description:Local and systemic immunosuppression are prominent features of pancreatic cancer, rendering anti-tumor effector cells inactive and immunotherapeutic approaches ineffective. The spleen, an understudied point of antigen-presentation and T cell priming in humans, holds particular importance in pancreatic cancer due to its proximity to the developing tumor. As main effectors of antigen presentation, dendritic cells display antigens to lymphocytes, thereby bridging the innate and adaptive immune response. While tumor-infiltrating anti-inflammatory dendritic cells have been described, splenic dendritic cells have historically just been considered to stimulate the anti-tumor immune response. Here, we describe, for the first time, the presence of an immunosuppressive, tolerogenic IDO1+ dendritic cell subset in the spleens of pancreatic cancer patients that likely contributes to systemic immunosuppression that is associated with pancreatic ductal adenocarcinoma. Network analysis of scRNA seq data reveals extensive communication networks between the identified tolerogenic DC cluster and numerous immune cell populations in the spleen. Interactions with innate and adaptive immune cells suggest a broad influence on leukocyte trafficking and immune regulation within the spleen microenvironment. The identification of signaling pathways involving AHR and IDO-1, CCL19, NECTIN2, CLEC2D, and others elucidates potential mechanisms underlying the immunosuppressive functions of this cell type.
2024-11-14 | GSE247635 | GEO
Project description:Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a cytosolic innate sensor of bacterial peptidoglycan, also functions in murine hematopoietic cells as a major regulator of both the generation and differentiation of lymphoid progenitors as well as peripheral T lymphocyte homeostasis. We further show that NOD1 mediates these functions by facilitating STAT5 signaling downstream of hematopoietic cytokines. In steady-state, loss of NOD1 resulted in a modest but significant decrease in numbers of mature T, B and NK cells. During systemic protozoan infection, this defect was markedly enhanced leading to host mortality. Lack of functional NOD1 also impaired T-cell-dependent anti-tumor immunity while preventing colitis. These findings reveal that in addition to its classical role as a bacterial ligand receptor, NOD1 plays an important function in regulating adaptive immunity through interaction with a major host cytokine signaling pathway.
2023-10-25 | GSE236485 | GEO
Project description:Background: Schistosomiasis remains an important global public health problem that affects 285 million people in 78 countries. The immune response mechanisms of host–parasite interaction are complex, and miRNAs play a major role in modulation of development, homeostasis, as well as the function of immune cells. Results: In this study, an miRNA microarray was applied to investigate differences in miRNA expression in splenic B cells of normal and 13w post infected mice. In total, 43 miRNAs were detected in splenic B cells of the C57BL/6 mice before and after infection, including 33 miRNAs with up-regulated expression, and 10 miRNAs with down-regulated expression in mice 13w infection with schistosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differentially expressed miRNAs revealed that many important biological pathways are triggered by schistosome infection in C57BL/6 mice, such as the Thyroid hormone signal pathway, Axon guidance, insulin signaling pathway, Pathways in cancer and Rap1 signaling pathway. The results reveal that miRNAs may be an important regulator of splenic B cells in the chronic phase of Schistosoma japonicum infection. Conclusions: The data presented here provide valuable information to increase understanding of the basic role of miRNAs in splenic B cells during the interaction of the S. japonicum with the host. This may be helpful in identifying the upstream molecular pathways controlling B cell specialization and provides a new platform of B cell manipulation to fine-tune their function.
2021-06-01 | GSE115443 | GEO
Project description:Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to “hallmark” processes impacting tumor development, in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally, protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74, and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation, operative through host age, that would indicate a modulation of host’s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression, carcinogenesis, and genetic perturbation by old age. For genome-wide expression profiling of tumor tissue, Mouse WG-6 BeadArray chips (Illumina, San Diego, CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion, Austin, TX) and labeled from all replicate biological samples for each condition. For spleen replicates, 9 spleen samples from adolescent with 0Gy , 10 from adolescent with 0.5Gyx3 protons, 9 from old from old with 0Gy, and 10 from old mice with 0.5Gyx3 protons, were used. All replicate samples were run individually. Total RNA was isolated and purified using TRIzol (Invitrogen) and quantified using an Agilent Bioanalyzer. Samples were deemed suitable for amplification and hybridization if they had 28s/18s = 2:1, RIN >7. Total RNA of 500ng per sample was amplified using AmbionTotalPrep, and 1.5ug of the product was loaded onto the chips. Following hybridization at 55C, the chips were washed and then scanned using the Illumina iScan System. The data was checked with GenomeStudio (Illumina) for quality control. Data were corrected through COMBAT correction, quantile normalized, collapsed to genes from probes, then imported into MultiExperiment Viewer, MeV for analysis. Statistically significant genes were determined by applying a one-way ANOVA with an adjusted Bonferroni correction and false discovery rate (FDR) < 0.001 that resulted in a list of significant genes.
2015-06-22 | E-GEOD-67243 | biostudies-arrayexpress