Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Disease
View SamplesThe lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.
Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.
Specimen part, Treatment
View SamplesThe role of paracrine/autocrine factors in inflammation, immune response and tumor development is well established. There is also an evidence that some of the cytokines there involved may participate in the regulation of the male gonads. However, their involvement in pathogenesis of male infertility has not been well defined yet. The aim of the present study was to examine the expression levels of IL-1 family members, IL-6, IL-10, TNF family, SCF and c-kit in infertile patients with idiopathic non-obstructive azoospermia (NOA) compared to men with normal spermatogenesis
The gene expression analysis of paracrine/autocrine factors in patients with spermatogenetic failure compared with normal spermatogenesis.
Sex, Specimen part
View SamplesThe aim of the dataset was to study on a genome-wide level the impact of Lat deficiency on gene expression in resting and activated CD4+ T cells
Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub.
Specimen part
View SamplesWe analyzed gene expression profiles of human testicular biopsies in men with idiopathic nonobstructive azoospermia. Using new generation oligonucleotide microarray platform GeneChip Human Gene 1.0 ST, we identified genes which could be potential biomarkers of azoospermia and molecular indicators that could determine a particular stage of impaired spermatogenesis. Thus, we shed light on genes which were had so far been weakly characterized and which were had never related to infertility before. These studies also included the comparative analysis of the hierarchical clustering of gene expression profile with histopathological data provided for azoospermic patients.
Potential biomarkers of nonobstructive azoospermia identified in microarray gene expression analysis.
Sex, Specimen part
View SamplesRecently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs. Overall design: RNA-seq of tumors from central nervous system primitive neuroectodermal tumor (CNS PNET) animal model
Stabilization of HIF-1α and HIF-2α, up-regulation of MYCC and accumulation of stabilized p53 constitute hallmarks of CNS-PNET animal model.
Specimen part, Disease stage, Subject
View SamplesPsoriasis is a chronic inflammatory skin disease of unknown etiology. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Topical application of Imiquimod, a Toll-like receptor 7 agonist, induces psoriasis in patients and psoriasiform inflammation in mice. We showed that daily application of Imiquimod for 14 days recapitulated both the initiation and the maintenance phase of psoriasis. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs and macrophages in the skin, we characterized their dynamics during both phases of psoriasis. During the initiation phase, neutrophils infiltrated the epidermis whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the maintenance phase, LCs and macrophage numbers increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by transcriptional analysis. Continuous depletion of LCs during the course of Imiquimod treatment aggravated chronic psoriatic symptoms as documented by an increased influx of neutrophils and a stronger inflammation. Therefore, by developing a mouse model that mimics the human disease more accurately, we established that LCs play a negative regulatory role during the maintenance phase of psoriasis.
Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
Specimen part, Treatment
View SamplesImmune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Cell line
View SamplesWe explored the connection between C/EBPa (CCAAT/enhancer binding protein a) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPa was expressed in human and murine intestinal epithelia in the transit amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APCMin/+ polyps, C/EBPa was absent from nuclear ß-catenin–positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPa KO in murine gut epithelia increased tumor volume. C/EBPa deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of ß-catenin in organoids attenuated C/EBPa expression. Comparing gene expression of wild type and C/EBPa KO organoids by RNA sequencing aimed to identify C/EBPa dependent alterations in gene expression. Overall design: These data suggest homeostatic and oncogenic suppressor functions of C/EBPa in the gut by restricting Wnt signaling.
A C/EBPα-Wnt connection in gut homeostasis and carcinogenesis.
Specimen part, Subject
View SamplesIn order to gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathway. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or 7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with 7/del(7q) by pathways involved in cell survival, whilst patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder thereby providing new targets for therapeutic intervention.
Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells.
Specimen part, Disease
View Samples