To test the hypothesis that defects in the termination of inflammatory signaling led to skin inflammation that results in the “Itchy” phenotype, we isolated RNA from the lesional skin of Itch-/- mice and from the skin of wild-type mice and performed genome-wide mRNA expression profiling by RNA sequencing. We ranked genes based on the fold change in their expression (increased or decreased) in Itch-/- skin relative to that in wild-type skin. The expression of several TNF–induced genes were increased in Itch-/- skin, including, IL-1ß, IL-6, IL-11, IL-19, IL-1RL1, CCL4, CXCL3, CXCL2, CCL3, and CD14. Overall design: mRNA profiles comparison between wild type (WT) skin and Itch-/- mice lesional skin
The E3 ubiquitin ligase Itch inhibits p38α signaling and skin inflammation through the ubiquitylation of Tab1.
No sample metadata fields
View SamplesNatural killer (NK) cells are NKp46+CD3- lymphocytes that can perform granule-dependent cytotoxicity and produce interferon-gamma, when isolated from blood, lymphoid organs, lung, liver and uterus. Here we identify in dermis, gut lamina propria and cryptopatches, very distinct populations of NKp46+CD3- cells with reduced ability to degranulate and to produce interferon-gamma. In gut, the transcription factor RORgamma-t and CD127 (IL-7R alpha) defined a novel subset of NKp46+CD3- that is reminiscent of lymphoid tissue inducer (LTi)-like cells. Gut ROR gamma t+NKp46+ cells produced IL-22 in contrast to ROR-gamma t-independent lamina propria and dermis NK cells. These data show that LTi-like cells and NK cells share unanticipated similarities and reveal the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.
Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin.
Sex, Age
View SamplesHuman rhinoviruses (HRV) are among the most common causes of respiratory infections in humans but can be frequently detected also in asymptomatic subjects. We evaluated the value of gene expression profiles to differentiate asymptomatic detection from symptomatic HRV infection in children.
Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesGlucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids, and compensatory glucagon hypersecretion involving expansion of pancreatic a-cell mass. Regulation of pancreatic a- and ß-cell growth has drawn a lot of attention because of potential therapeutic implications. Recent findings indicate that hyperaminoacidemia triggers pancreatic a-cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative a-cells, and that Slc38a5 is critical for the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased a-cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino acid-dependent regulation of pancreatic a-cell mass in mice. Overall design: Examination of the transcriptomes of pancreatic islets of mice treated with GCGR-antibody and an isotype control antibody.
Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.
Specimen part, Cell line, Subject
View SamplesGlucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic a cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic a cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative a cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased a cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino-acid-dependent regulation of pancreatic a cell mass in mice. Overall design: Examination of the transcriptomes of islet non-beta-cells of GcgR knock out mice.
Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.
Sex, Specimen part, Cell line, Subject
View SamplesObjective: Physical exercise and vitamin E are considered effective treatments of nonalcoholic fatty liver and other metabolic diseases. However, vitamin E has also been shown to interfere with the adaptation to exercise training, in particular for the skeletal muscle. Here, we studied the hypothesis that vitamin E also interferes with the metabolic adaptation of the liver to acute exercise.
A Vitamin E-Enriched Antioxidant Diet Interferes with the Acute Adaptation of the Liver to Physical Exercise in Mice.
Sex, Specimen part
View SamplesPatients with HIV-associated TB are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 63 patients with HIV-associated TB, 33 of whom developed TB-IRIS. Of which transcriptomic profiling was performed using longitudinal whole blood RNA samples from 15 non-IRIS and 17 TB-IRIS patients. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified as early as week 0.5 (2-5 days post-ART) and predicted a downstream activation of proinflammatory cytokines. At the peak of IRIS (week 2), transcriptomic signatures were overrepresented by innate receptor signaling pathways including toll-like receptor, IL-1 receptor and TREM-1.
HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling.
Specimen part
View SamplesThe objective of this study is to: 1) Characterize the innate immune responsiveness of patients with inborn errors in Toll-IL1 receptor signaling pathway (IRAK4, MyD88 deficiencies) compared to healthy subjects, through the analysis of blood leukocytes' transcriptional profiles after stimulation with ligands for the whole set of Toll-like receptors and IL-1Rs plus whole bacteria. 2) Understand the redundancies in TLR pathway in humans. 3) Explore the use of blood profiling approaches to assess the immune status of an individual by using Primary Immune Deficiencies as a proof of principle.
A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.
Sex, Race
View SamplesEmbryonic mouse brain development involves a sequential differentiation of multipotent progenitor cells into neurons and glia. Using microarrays and large 2-D electrophoresis, we investigated the transcriptome and proteome of mouse brains at embryonic days 9.5, 11.5 and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between the time points investigated but interestingly, the rate of alteration was about 10% to 13% of all proteins and mRNAs during every two days of development. Furthermore, up- and downregulation was balanced. This was confirmed for two additional stages of development, embryonic day 16 and 18. We hypothesize that during embryonic development, the rate of protein expression alteration is rather constant due to a limitation of cellular resources such as energy, space and free water. The similar complexity found at the transcriptome and proteome level at all stages suggests, that changes in relative concentration of gene products rather than an increased number of gene products dominate throughout cellular differentiation. We found that metabolism and cell cycle related gene products were downregulated in expression when precursor cells switched from proliferation to neuronal differentiation (day 9.5 to 11.5), whereas neuron specific gene products were upregulated. A detailed analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch and Wnt signaling pathways.
Transcriptome and proteome analysis of early embryonic mouse brain development.
No sample metadata fields
View SamplesUpon induction of DNA damage Arabidopsis thaliana plants initiate a transcriptional response program governed by signalling cascades which are activated by the ATM and ATR kinases
GMI1, a structural-maintenance-of-chromosomes-hinge domain-containing protein, is involved in somatic homologous recombination in Arabidopsis.
Specimen part
View Samples