The development of chemo-resistance has dramatically limited the clinical efficiency of platinum-based therapy. Although many resistant mechanisms have been demonstrated, genetic/molecular alterations responsible for drug resistance in the majority of clinical cases has not been identified.
The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers.
No sample metadata fields
View SamplesWe have analyzed the effects of IL-21 signaling on T cell activation, IL-22 production and gut inflammation
IL-21 induces IL-22 production in CD4+ T cells.
Age, Specimen part, Treatment
View SamplesWe have analyzed the effects of IL-27 signaling in dendritic cells (DCs) in the activation and polarization of effector and regulatory T cells, and the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis.
IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39.
Age, Specimen part, Treatment
View SamplesNon-switched memory (ME-M) B cells are an enigmatic population of IgM+ memory lymphocytes that are thought to emerge from germinal centers during systemic antibody responses against T cell-dependent antigens. To gain new insights into the properties of ME-M B cells generated during intestinal antibody responses, we performed global gene transcriptome expression analysis on nave, ME-M and canonical memory class-switched (ME-SW) B cells purified from human gut samples. Marginal zone (MZ) and ME-SW B cells isolated from human spleen samples were used for comparison.
Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals.
Specimen part
View SamplesUnderstanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor gammat (RORgammat) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We identified a novel cell subset of CD56dimNKp46low cells that includes RORgammat+ILCs with a lineage-CD94-CD117brightCD127bright phenotype.We also included data regarding the genome-wide transcriptional profiles of human healthy colonic NK cells and RORgammat+ILCs.The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.
Mapping of NKp46(+) Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues.
Specimen part
View SamplesPeroxisome proliferator-activated receptor beta/delta protects against obesity by reducing dyslipidemia and insulin resistance via effects in various organs, including muscle, adipose tissue, liver, and heart. However, nothing is known about the function of PPAR-beta in pancreas, a prime organ in the control of glucose metabolism. To gain insight into so far hypothetical functions of this PPAR isotype in insulin production, we specifically ablated Ppar-beta in pancreas. The mutated mice developed a chronic hyperinsulinemia, due to an increase in both beta-cell mass and insulin secretion. Gene expression profiling indicated a broad repressive function of PPAR-beta impacting the vesicular compartment, actin cytoskeleton, and metabolism of glucose and fatty acids. Analyses of insulin release from the islets revealed an increased second-phase glucose-stimulated insulin secretion. Higher levels of PKD, PKC-delta and diacyglycerol in mutated animals lead to an enhanced formation of trans-Golgi network (TGN)-to-plasma-membrane transport carriers in concert with F-actin disassembly, which resulted in increased insulin secretion and its associated systemic effects. Taken together, these results provide evidence for PPAR-beta playing a repressive role on beta-cell growth and insulin exocytosis, which shed new light on its anti-obesity action.
PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice.
Age, Specimen part
View SamplesWe elucidate a neurological syndrome affecting both the PNS and CNS defined by CLP1 mutations that impair tRNA splicing Overall design: Identification and biochemical characterization of mutant CLP1 in human patients
Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.
No sample metadata fields
View Samples