Tolerogenic dendritic cells (DCs) induce regulatory T-cells and dampen pathogenic T-cell responses. Hereby, they have gained interest as a therapeutic target in the combat against autoimmune diseases. In this study we investigated whether tolerogenic DCs are induced by the phytonutrient carvacrol, a molecule with known anti-inflammatory properties. In this study, bone marrow derived DCs were treated with carvacrol in combination with thermal stress. Gene expression profiles were obtained by microarray analysis to test for an induced tolerogenic phenotype. To investigate the tolerogenic properties of treated DCs in vivo, T-cell anergy or the induction of a regulatory T-cell phenotype was studied in antigen specific T-cells. Finally, treated DCs were tested by transfer into an experimental arthritis model.
Tolerogenic dendritic cells that inhibit autoimmune arthritis can be induced by a combination of carvacrol and thermal stress.
Sex, Age, Specimen part, Compound
View SamplesAnalysis of tissues of DBA/2 mice fed a standard breeding diet (SBD) and high fat diet (HFD) revealed tissue specific roles in inflammation and disease, and altered communication between tissues. The tissues surveyed incuded adipose tissues (brown, inguinal, mesenteric, retro-peritoneal, subcutaneious and gonadal), muscle and liver.
High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.
Specimen part, Treatment
View SamplesThe link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.
Sex, Specimen part
View SamplesLymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
Specimen part, Subject
View SamplesWe performed micrarrays to investigate neuronal gene expression changes during acute inflammatory CNS axon injury using the murine myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) model. The present study was assigned to assess the direct and indirect endogenous neuronal response to spinal axonal injury in the motor and sensory cortex.
Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Specimen part, Disease stage, Time
View SamplesTransgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Specimen part, Disease stage
View SamplesTransgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Specimen part, Time
View SamplesHepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miR, resulted in significant de-repression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis and necrosis was noted in anti-miR-21 treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21
Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation.
Cell line
View Samplesperipheral blood samples of two leukemia patients in remission were profiled by single cell RNA sequencing approximately 1 year after receiving WT1 specific transgenic T cell therapy, at a time when patients were in clinical remission Overall design: single cell RNA sequencing of peripheral blood mononuclear cells
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Specimen part, Disease, Subject
View Samples