Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in immunomodulation in different murine models in which these cells participate. The fate of the CD4 T cells activated in the presence of the immunosuppressor or its long-term effects on these cells are however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished antibody production against specific and unrelated antigens. Transcriptionally, the salivary protein provokes a sharp acute effect that includes known activation factors, such as Il2, Cd44, or Il2ra, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with the immunomodulatory protein does not result in B cell anergy or the generation of myeloid suppressor cells. However, the immunomodulatory protein induces the increased expression of the ectoenzyme, CD73, in regulatory T cells. Our results suggest that the specific regulation of CD73, a known modulator of adenosine levels, by Salp15 results in long-term cross-antigenic immunomodulatory effects. Overall design: Genome-wide changes in gene Expression in mouse CD4 T cells activated with anti-CD3/CD28 in the presence of 25 ug/mL of the tick salivary protein, Salp15 or its inactive control (Salp15deltaP11) were generated by RNAseq.
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.
Age, Specimen part, Cell line, Treatment, Subject, Time
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A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Age, Specimen part, Treatment
View SamplesMacrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Specimen part, Treatment
View SamplesMacrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response. Overall design: Genome-wide changes in gene Expression in mouse bone marrow-derived macrophages stimulated with Borrelia burgdorferi or left unstimulated were generated by RNAseq.
Regulation of macrophage activity by surface receptors contained within Borrelia burgdorferi-enriched phagosomal fractions.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesBovine papillomavirus (BPV) is the causative agent of papillomatosis in cattle. The disease causes cutaneous and mucosal lesions that can be minimized or lead to the appearance of malignant tumors. This study aims to identify possible molecular mechanisms that are behind the pathological processes associated with bovine papillomatosis through the identification of genes related to the development of the lesions. For this, next-generation RNA sequencing was used to assess differentially expressed genes in infected by BPV and non-infected bovines. Three animals with papillomatosis lesion and three without papillomatosis lesion were studied. The Galaxy platform was used to analyze the data generated by the sequencing. The Illumina output files were converted to FASTQ format. Quality evaluation was performed using FastQC and the sequence quality cut was performed using Trimmomatic. TopHat and Bowtie were used to map and align the reads with the reference genome. The abundance of the expressed genes was verified using Cuffilinks. Cuffdiff was used for differential expression analysis. Functional annotation of the differentially expressed genes was performed using Gene Ontology (GO) databases. RNA-sequencing generated a total of 121,722,238 of reads. In the gene expression analysis, a total of 13,421 genes expressed were identified and of these 1343 were differentially expressed. The functional annotation of differentially significant genes showed that many genes presented functions or they were related to metabolic pathways associated with the progression of papillomatosis lesions and cancer development in cattle. Although more studies are needed, this is the first study that focused on a large-scale evaluation of gene expression associated with the BPV infection, which is important to identify possible mechanisms regulated by the host genes that are necessary the development of the lesion Overall design: Analysis of three BPV infected and three BPV non-infected samples
Comparative transcriptomic analysis of bovine papillomatosis.
Age, Specimen part, Treatment, Subject
View SamplesThe development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Specimen part, Cell line, Subject
View SamplesWe deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.
Age, Specimen part
View SamplesThe global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sex
View SamplesReactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Genomic analysis of reactive astrogliosis.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sex, Specimen part, Subject
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