Hyper IgE Recurrent Infection Syndrome (HIES or Jobs syndrome), is a rare disorder of immunity and connective tissue, typically manifest with boils, cyst-forming pneumonias, and extremely elevated serum IgE as well as retained primary dentition and bone abnormalities. Inheritance can be autosomal dominant.
STAT3 mutations in the hyper-IgE syndrome.
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View SamplesPhosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sex, Specimen part, Time
View SamplesBone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).
NF-κB1 inhibits TLR-induced IFN-β production in macrophages through TPL-2-dependent ERK activation.
Specimen part
View SamplesBacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death.
Late multiple organ surge in interferon-regulated target genes characterizes staphylococcal enterotoxin B lethality.
Sex, Specimen part
View SamplesAnalysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623 Overall design: Young adult female mGFAP-Cre-RiboTag or mGFAP-Cre-RiboTag-STAT3-LoxP mice underwent severe crush SCI at thoracic level 10. 14 days following SCI, the central 3mm of the SCI lesion was extracted, homogenized and (i) astrocyte-specific ribosome-associated RNA (ramRNA) precipitated via a hemagglutinin (HA) tag targeted to either WT (n=4) or STAT3-CKO (n=3) astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples. Sex and age-matched mGFAP-Cre-RiboTag mice served as uninjured controls (n=4).
Astrocyte scar formation aids central nervous system axon regeneration.
Specimen part, Subject
View SamplesSalmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of this gram-negative bacteria in such pigs is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we have initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n=40) was inoculated with ST and the peripheral blood and feces were collected between 2 and 20 days post-inoculation. Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. The global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip?analysis of peripheral blood RNA at day 0 and day 2 post-inoculation.
Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: intersection of IFNG, TLR and miRNA pathways.
Specimen part
View SamplesHost defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb or IFNg treatment in wild typ and Irf9-/- bone marrow derived macrophages. Overall design: Methods: Bone marrow derived macrophage mRNA of wild-type (WT) and Irf9 knock out mice (IRF9-/-) untreated, as well as 2h IFNb and IFNg treated were generated by deep sequencing, in triplicate, using Illumina sequencing.
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Specimen part, Cell line, Treatment, Subject
View SamplesThe activation of vascular smooth muscle cells (VSMCs) during hypertension-induced arterial remodeling processes relies on a change of the gene expression program, i.e., up-regulation of genes to induce migration, proliferation and matrix degradation/synthesis. At the same time, genes controlling the quiescent, contractile VSMC phenotype are down-regulated. We used microarrays to detail the global program of gene expression underlying hypertension-induced vascular remodeling in the presence and absence of regulator of G-protein signaling 5 (RGS5) and identified distinct classes of down-regulated genes during vascular remodeling when RGS5 was not present.
Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5.
Sex, Specimen part, Treatment
View SamplesHost defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb treatment in wild type and Irf9-/- mouse embryonic fibroblasts. Overall design: Methods: Mouse embryonic fibroblast (MEF) mRNA of wild-type (WT) and Irf9 knock out mice (IRF9-/-) untreated, as well as 2h IFNb treated were generated by deep sequencing, in triplicate, using Illumina sequencing.
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Subject
View SamplesHost defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb treatment in wild type and Irf9-/- THP1 cells. Overall design: Methods: mRNA of untreated and IFNb treated wild-type (WT) and Irf9 knock out (IRF9-/-) human monocytic THP1 cells were analyzed by deep sequencing, in triplicate, using Illumina sequencing.
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Subject
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