Gene expression profile of human antigen presenting cells with a tolerogenic phenotype
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE98480 | GEO | 2017/05/03
SECONDARY ACCESSION(S): PRJNA385188
REPOSITORIES: GEO
Similar Datasets
Project description:The human immune system evolves gradually from the embryo to adult, continuously adapting to the ever-changing environment of the human body. The ability of our immune system to sense external cues and adapt as we develop is as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DC), professional antigen sensing and presenting cells, play a crucial role in such processes as sentinels of the immune system, initiating and regulating immune responses. We have previously characterised CD14+ DC, CD1c+DC and CD141+DC subset by flow cytometry and microarray transcriptome analysis in adult mucosal tissues, and have described their superior abilities to either induce IL-17 responses or to cross-present external antigens respectively. However, the role of such DC subsets in the tolerogenic environment of the fetus remains undefined, prompting us to investigate the ontogeny and functional significance of human fetal DCs.
2017-06-28 | GSE85304 | GEO
Project description:We found in our study that NCoR1 knock down dendritic cells (DCs) develop tolerogenic behavior upon activation and these cells have the potential to modulate T helper cell differentiation toward Treg phenotype. Here to understand the mechanism of this process we performed NCoR1 ChIP-seq in wild type DCs before and after CpG ligand activation and transcriptome analysis of NCoR1 KD DCs to identify the direct and indirect target genes. We also predicted PU.1 as the recruting factor for NCoR1 in DCs based on motif enrichment and later on validated that by performing PU.1 ChIP-seq in control and NCoR1 KD DCs.
2019-10-18 | GSE110421 | GEO
Project description:Little is known about the early transcriptional events in innate immune signaling in immature and tolerogenic monocyte-derived dendritic cells (DCs), the professional antigen-presenting cells of our immune system. TLR ligands usually induce a proinflammatory transcriptional response, whereas IL10 and/or dexamethasone induce a more tolerogenic phenotype. We used Affymetrix microarrays to obtain detailed information underlying pro- and anti-inflammatory transcriptional responsesand transcriptional networks in DCs
2011-07-08 | GSE23371 | GEO
Project description:Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists.. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h
2007-09-14 | E-GEOD-2706 | biostudies-arrayexpress
Project description:Little is known about the early transcriptional events in innate immune signaling in immature and tolerogenic monocyte-derived dendritic cells (DCs), the professional antigen-presenting cells of our immune system. TLR ligands usually induce a proinflammatory transcriptional response, whereas IL10 and/or dexamethasone induce a more tolerogenic phenotype. We used Affymetrix microarrays to obtain detailed information underlying pro- and anti-inflammatory transcriptional responsesand transcriptional networks in DCs A pilot experiment was performed in which monocyte-derived DCs were either treated with TLR4 ligand LPS, or IL10 and dexamethason. Furthermore, IL10/dexamethason treated cells were also stimulated with LPS for an additional 6 hr. All samples were then subjected to global gene expression analysis using Affymetrix technology.
2011-07-08 | E-GEOD-23371 | biostudies-arrayexpress
Project description:Human monocyte-derived dendritic cells (moDCs) have been used as an in vitro model for studying tolerance and immunity. However, the underlying metabolic states of tolerogenic (dexamethasone and vitamin D3-treated), immature and immunogenic (mature, LPS-treated) moDCs have not been completely characterized. Through transcriptomic analyses, we determined that tolerogenic moDCs exhibit augmented catabolic pathways with respect to oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis. Functionally, tolerogenic moDCs showed the highest mitochondrial membrane potential, production of reactive oxygen species and superoxide, and increased mitochondrial spare respiratory capacity. Tolerogenic and mature moDCs manifested differential FAO gene expression with FAO activity being significantly higher in tolerogenic and immature moDCs than in mature. In addition, tolerogenic and mature moDCs demonstrated similar levels of glycolytic rate, but not glycolytic capacity and reserve, which were more pronounced in tolerogenic and immature moDCs. Finally, tolerogenic and immature moDCs, but not mature moDCs, showed high plasticity to compensate the intracellular ATP content after inhibition of different energetic metabolic pathways. Overall, tolerogenic moDCs exhibit a metabolic signature of increased, stable OXPHOS programing and high plasticity for metabolic adaptation. These findings provide a framework for future research of metabolic properties of human DCs.
2015-05-08 | GSE52894 | GEO
Project description:We use tolDCs from syngeneic (C57BL6) and allogeneic (BALB/c) mice to show potent renoprotective abilities in a ischemia reperfusion AKI model. Dendritic cells were derived from mice bone marrow and cultured for 7 days with GM-CSF and IL-4. Tolerogenic DCs were cultured in the same DC media but with the addition of VitD3 and IL10. LPS was added on day 6 and cells harvested for use or analysis on day 7.
2023-07-01 | GSE205322 | GEO
Project description:Microarray analysis of miRNAs from CD4 T cells after their encounter with DCs in the presence of the antigen vs the absence
2017-08-15 | GSE85363 | GEO
Project description:Human monocyte-derived dendritic cells (moDCs) have been used as an in vitro model for studying tolerance and immunity. However, the underlying metabolic states of tolerogenic (dexamethasone and vitamin D3-treated), immature and immunogenic (mature, LPS-treated) moDCs have not been completely characterized. Through transcriptomic analyses, we determined that tolerogenic moDCs exhibit augmented catabolic pathways with respect to oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis. Functionally, tolerogenic moDCs showed the highest mitochondrial membrane potential, production of reactive oxygen species and superoxide, and increased mitochondrial spare respiratory capacity. Tolerogenic and mature moDCs manifested differential FAO gene expression with FAO activity being significantly higher in tolerogenic and immature moDCs than in mature. In addition, tolerogenic and mature moDCs demonstrated similar levels of glycolytic rate, but not glycolytic capacity and reserve, which were more pronounced in tolerogenic and immature moDCs. Finally, tolerogenic and immature moDCs, but not mature moDCs, showed high plasticity to compensate the intracellular ATP content after inhibition of different energetic metabolic pathways. Overall, tolerogenic moDCs exhibit a metabolic signature of increased, stable OXPHOS programing and high plasticity for metabolic adaptation. These findings provide a framework for future research of metabolic properties of human DCs. Total RNA of sixteen samples from four moDC types (tolerogenic, LPS-tolerogenic, immature and mature) were extracted by Trizol (Invitrogen) followed by a clean-up procedure using RNeasy Micro Kit (Qiagen). All RNA samples had an integrity number ≥9.6 assessed by Agilent Bioanalyzer. Total RNA samples were amplified using TargetAmp™ and the biotinilated cRNA was prepared by Nano-g™ Biotin-aRNA Labeling Kit for the Illumina® System (Epicentre). After the hybridization to the Illumina Human HT-12 v4 Beadchips for 17 h at 58°C, the arrays were washed, stained (Illumina Wash Protocol) and then scanned using BeadArray Scanner 500GX. Array data were extracted at the probe level without background correction using Illumina GenomeStudio software. These raw data were quantile normalized and log2 transformed. Technical replicates were obtained from the hybridization in duplicate of three samples. Pearson correlation analysis showed high correlation between the technical replicates (r>0.99). Differentially expressed genes (DEGs) were identified using Limma16 with Benjamini-Hochberg multiple testing correction (p<0.05). DEGs were further clustered into different groups according to the patterns of expression change among the different moDC types using STEM software17. The analysis was performed in R v.2.12.2 (http://www.R-project.org) with Bioconductor 2.12 (http://www.bioconductor.org) and enabled by Pipeline Pilot (www.accelrys.com).
2015-05-08 | E-GEOD-52894 | biostudies-arrayexpress
Project description:Tolerance to self- or innocuous foreign antigens is vital for preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing AutoImmune Regulator, Aire, play a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development. A second wave of Treg cell differentiation occurs in the periphery, upon exposure to dietary and commensal microbiota derived antigens within the first few weeks of life, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells are not known. Here we identified a new lineage of tolerogenic RORγt+ antigen-presenting cells (APC) with a hybrid dendritic cell (DC)-mTEC phenotype, dubbed Thetis cells (TCs), comprising 4 major sub-groups (TC I-IV), We uncovered a developmental wave of TCs within intestinal lymph nodes during a critical early life window, coincident with the wave of pTreg cell differentiation. While Aire+ TC I and III bore remarkable homology with Aire+ mTECs, including expression of tissue restricted self-antigens, TC IV lacked Aire expression and were enriched for molecules required for pTreg generation, including the TGF-β activating integrin αvβ8. Loss of either MHCII or Itgb8 expression by TCs led to a profound impairment in intestinal pTreg differentiation, with onset of intestinal inflammation. In contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical DCs was neither sufficient nor required for pTreg generation, further implicating TCs as the critical tolerogenic RORγt+ APC. Our studies reveal parallel pathways for establishment of tolerance to self and foreign antigen within the thymus and periphery, marked by involvement of shared cellular and transcriptional programs.
2022-09-06 | GSE174405 | GEO