Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished—training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral beta-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology. Overall design: mRNA was isolated from FACS-purified microglia and prepared for RNA-sequencing.
Innate immune memory in the brain shapes neurological disease hallmarks.
Sex, Specimen part, Treatment, Subject
View SamplesThe perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Remodeling the cardiac transcriptional landscape with diet.
Sex, Specimen part
View SamplesA soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sex, Specimen part
View SamplesMicroarrays were used to assess gene expression in patients with ET, PV, and PMF before and after treatment with IFNalpha2 in a paired design.
The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe goal is the characterization of the off-target activity of BKM120 observed in A2058 human melanoma cell line at IC90 concentration (3.606 M) but not at lower concentrations. Controls are BEZ235, GDC0941, showing no off-target activity.
Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations.
Cell line
View SamplesDiagnosis of inflamed human orbit tissue with standard clinical and histopathology evaluation data is imprecise. A large number of these patients are diagnosed with the catch-all classification of nonspecific orbital inflammation (NSOI).
Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.
Sex, Specimen part, Disease
View SamplesWe Report the genome-wide RNA expression levels in control and schizophrenia hiPSC dervied NPC treated with neuronal media for 2 days. In total about 15,000 gene expression were detected in all samples, of which 1349 were dysregualted. Overall design: Examination, identification and comparision of mRNA expression profliles in control and schizophrenia npc
Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).
Specimen part, Subject
View SamplesUbiquitylation plays an important role in the control of Na+ homeostasis by the kidney. It is well established that the epithelial Na+ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney, and is also a circadian output gene. In heterologous expression systems USP2-45 binds to ENaC, deubiquitylates it and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na+ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that the USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences to wild-type littermates with respect to the diurnal control of Na+ or K+ urinary excretion and plasma levels neither on standard diet, nor after acute and chronic changes to low and high Na+ diets, respectively. Moreover, they had similar aldosterone levels either at low or high Na+ diet. Blood pressure measurements using telemetry did not reveal variations as compared to control mice. Usp2-KO did neither display alternations in ENaC or Na+,Cl--cotransporter (NCC) expression, nor were there any changes in regulatory protein levels, as evidenced by immunoblotting and transcriptome analysis. We conclude that USP2-45 is not crucial for the regulation of Na+ balance or maintenance of blood pressure in vivo.
Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure.
No sample metadata fields
View SamplesPlasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells.
Specimen part
View SamplesSarcoidosis + Follow-up 6 month after
Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
No sample metadata fields
View Samples