The IFN type I signature is present in over half of primary Sjgrens syndrome (pSS) patients and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered to be the source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of pSS patients.
Contrasting expression pattern of RNA-sensing receptors TLR7, RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary Sjögren's syndrome.
Sex, Specimen part, Disease, Disease stage
View SamplesAims: establishment of reference samples to investigate gene expression selective for endocrine or ductal-exocrine cells within the adult human pancreas. To this end, human islet endocrine cells, FACS-enriched in insulin+ cells, (n=3) and human exocrine ductal cells (n=2) are compared on Affymetrix HG133A platform with duplicate hybridizations of a panel of other primary human tissues.
Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.
Specimen part
View SamplesThe study was designed to capture the in vivo adaptations of nutrient-sensing pancreatic beta cells to fed or fasted (24h) state.
Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.
No sample metadata fields
View SamplesThe phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.
No sample metadata fields
View SamplesAbstract Two major dendritic cell (DC) subsets have been described in the islets of mice: The immunogenic CD8-CD11b+ DCs and the tolerogenic CD8+CD103+ DCs. We have recently reported on reduced numbers of the minor population of tolerogenic CD8+CD103+ DCs in the pancreas of 5 week old pre-diabetic non-obese diabetic (NOD) mice. Aim: To analyze also the larger subset of CD11c+CD8- DCs isolated from the pancreas of pre-diabetic NOD mice 1) for maturation and tolerance inducing molecules found abnormally expressed on CD8+CD103+ DCs, and 2) for genome-wide gene expression to further elucidate abnormalities in underlying gene expression networks. Methods: CD11c+CD8- DCs were isolated from 5 week old C57BL/6 and NOD pancreas. Expression of cell surface markers including CD86, CCR5, CD11b, CD103, Clec9a, CD24 and CD200R3 were measured by FACS. Genome-wide gene expression by microarray was assessed during the steady state and after in vitro LPS stimulation. Results: The steady state pancreatic CD11c+ CD8- DCs during the pre-diabetic stage showed: 1) A reduced expression of several gene networks important for the prime functions of the cell, such as for cell renewal, immune stimulation and immune tolerance induction, for migration and for the provision of growth factors for beta cell regeneration. This general deficiency state was corroborated by a reduced in vivo proliferation (BrdU incorporation) of the cells and the reduced expression in FACS analysis of CD86, CCR5, CD103, Clec9a, CD24 and CD200R3 on the cells. 2) A hyper reactivity of these cells to LPS correlated with an enhanced pro-inflammatory state characterized by altered expression of a number of classical pro-inflammatory factors and cytokines. Conclusion: The NOD CD11c+CD8- DCs seem to be Janus-faced depending on the conditions: Deficient in steady state with reduced immune stimulation capabilities also for tolerance induction; over-inflammatory with a molecular profile suggesting a preferential stimulatory capacity for Th1 cells when encountering a Pathogen-Associated Molecular Pattern (PAMP) in the form of LPS.
The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
Sex, Age, Specimen part, Treatment
View SamplesThe Eol1 cell line has been derived from a patient with chronic eosiniphilic leukemia. Eol1 cells express the FIP1L1-PDGFRalpha oncogene. Inhibition of FIP1L1-PDGFRalpha with imatinib mesylate (Glivec) blocks proliferation and survival of the cells. We performed microarray expression analysis to identify genes specifically regulated by FIP1L1-PDGFRalpha using imatinib-treated cells as baseline. The list of regulated genes was consistent with the activation of STAT trancription factors by FIP1L1-PDGFRA.
Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data.
Cell line, Treatment
View SamplesBackground
Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.
Time
View SamplesDespite wide scale vaccination with Mycobacterium bovis BCG, the prevalence of tuberculosis remains high, reflecting the global variable efficacy of this vaccine against adult pulmonary TB. Characterisation of different immune responses to M. tuberculosis and M. bovis BCG would increase understanding of pathology following M. tuberculosis infection or reactivation, and would facilitate the rational design of a new vaccine. Gene expression profiling was conducted on samples from diluted whole blood cultures from three healthy donors following incubation with live mycobacteria for six days. Approximately 8,000 gene entities were at least two-fold up- or down- regulated by the mycobacteria, and both mycobacteria induced similar expression changes in approximately 2,300 genes. Strikingly, many genes exhibited qualitatively different expression patterns, with over 1,000 genes up-regulated in response to M. bovis BCG but not changed by M. tuberculosis. Gene Ontology analysis revealed that the genes which failed to upregulate in M. tuberculosis-infected cultures included a large proportion of genes with lysosomal function. The inhibited up-regulation of expression of IFN--inducible protein 30, acid phosphatase 2, cathepsin B and GM2 ganglioside activator was verified in samples from six biologically independent donors by qRT-PCR. The failure to up-regulate these genes in response to M. tuberculosis may constitute an immune evasion mechanism, preventing intracellular killing and antigen presentation.
Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.
Specimen part
View SamplesBackground Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips, to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity.
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response.
Specimen part, Disease, Subject, Time
View Samples