Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 productionex vivoby LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.
Specimen part, Treatment
View SamplesObjective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients.
Gene expression in peripheral blood mononuclear cells from children with diabetes.
Sex, Age, Treatment, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesGlucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma - excessive ASM growth are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as interleukin 1beta and tumor necrosis factor alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and interleukin 1beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis.
Glucocorticoid- and protein kinase A-dependent transcriptome regulation in airway smooth muscle.
No sample metadata fields
View SamplesWith particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR.
The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesThis dataset was used to establish whole blood transcriptional modules (n=260) that represent groups of coordinately expressed transcripts that exhibit altered abundance within individual datasets or across multiple datasets. This modular framework was generated to reduce the dimensionality of whole blood microarray data processed on the Illumina Beadchip platform yielding data-driven transcriptional modules with biologic meaning.
Interferon signature in the blood in inflammatory common variable immune deficiency.
Disease
View SamplesA detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.
Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.
Sex, Age, Specimen part
View Samples