Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1033837 | ENA |
REPOSITORIES: ENA
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Project description: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.
2012-01-16 | E-MEXP-3489 | biostudies-arrayexpress
Project description:We compared migratory DCs in draining mediastinal lymph node after intranasal administration of different vaccine adjuvants based on CTA1 subunit of cholera toxin. The goal was to determine different characteristics of dendritic cells subsets after pro-inflammatory vs tolerogenic adjuvant. We had 3 groups: CTA1-DD (pro- inflammatory), CTA1(R7K)-DD (tolerogenic) and PBS to define DC which migrate to LN. All vaccine constructs included 3Ea peptide to allow for sorting of DC which took up the vaccine.
2023-05-15 | E-MTAB-12942 | biostudies-arrayexpress
Project description:hBcl-2 transgene under CD11c promotor fosters tolerogenic DCs properties linked to a global downmodulation of genes related to pro-inflammatory pathway and upregulation of tolerogenic ones We used microarrays to detail the global programme of gene expression underlying the tolerogenic phenotype of hBcl-2 expressing CD103+ CD11b+ cDCs to identify the pathways involved in the promotion of tolerogenic DCs ability
2021-02-17 | GSE166899 | GEO
Project description:Although much is known on the transcriptional profiles of dendritic cells (DCs) during maturation, the molecular switches critical for the acquisition of a tolerogenic program by DCs are still obscure. In the present study, we explored the gene expression pattern of CD8+ DCs purified from the mouse spleen and treated with interferon (IFN)-gamma. The cytokine, indeed, potentiates the tolerogenic potential of this DC subset via induction of the immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO). By comparing the expression of the IFN-gamma-modulated genes in IDO+ versus IDO- murine DCs, we found a consistent and selective association of the IDO-competent phenotype with the down-modulation of the Tyrobp gene, encoding the adapter molecule DAP12. IFN-gamma-mediated down-modulation of this gene involved IFN consensus sequence binding protein (ICSBP), a transcription factor also known as IRF-8. While silencing of Tyrobp conferred IDO functional competence on IDO- DCs, silencing of Icsbp1 in IDO+ cells completely abolished IDO expression and function. In parallel, silencing of TYROBP conferred IDO competence on human IDO- DCs while silencing of IRF8 impaired IDO expression and activity in human IDO+ DCs. Therefore, the same small set of molecular switches controls IDO competence in murine and human DCs. Keywords: Time-course, treatment with agent (IFN-gamma)
2005-12-09 | GSE3337 | GEO
Project description:Depending on how an antigen is perceived, dendritic cells (DCs) mature in an immunogenic or tolerogenic manner, safeguarding the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well characterized, the signals driving tolerogenic maturation in homeostasis are still poorly understood. Here we demonstrate that engulfment of apoptotic cells triggers homeostatic maturation of conventional cDC1s in the spleen. This process can be modeled by engulfment of empty, non-adjuvanted lipid nanoparticles (LNPs), is marked by intracellular accumulation of cholesterol, and highly unique to type 1 DCs. Engulfment of apoptotic cells or cholesterol-rich LNPs leads to activation of the LXR pathway driving cellular cholesterol efflux and repression of immunogenic genes. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs represses the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell immunity. These data demonstrate how DCs exploit the conserved cellular cholesterol efflux pathway to regulate induction of tolerance or immunity and reveal that administration of non-adjuvanted cholesterol-rich LNPs is a powerful platform for inducing tolerogenic DC maturation.
2023-03-30 | GSE228544 | GEO
Project description:Depending on how an antigen is perceived, dendritic cells (DCs) mature in an immunogenic or tolerogenic manner, safeguarding the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well characterized, the signals driving tolerogenic maturation in homeostasis are still poorly understood. Here we demonstrate that engulfment of apoptotic cells triggers homeostatic maturation of conventional cDC1s in the spleen. This process can be modeled by engulfment of empty, non-adjuvanted lipid nanoparticles (LNPs), is marked by intracellular accumulation of cholesterol, and highly unique to type 1 DCs. Engulfment of apoptotic cells or cholesterol-rich LNPs leads to activation of the LXR pathway driving cellular cholesterol efflux and repression of immunogenic genes. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs represses the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell immunity. These data demonstrate how DCs exploit the conserved cellular cholesterol efflux pathway to regulate induction of tolerance or immunity and reveal that administration of non-adjuvanted cholesterol-rich LNPs is a powerful platform for inducing tolerogenic DC maturation.
2023-03-30 | GSE228523 | GEO
Project description:Although much is known on the transcriptional profiles of dendritic cells (DCs) during maturation, the molecular switches critical for the acquisition of a tolerogenic program by DCs are still obscure. In the present study, we explored the gene expression pattern of CD8+ DCs purified from the mouse spleen and treated with interferon (IFN)-gamma. The cytokine, indeed, potentiates the tolerogenic potential of this DC subset via induction of the immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO). By comparing the expression of the IFN-gamma-modulated genes in IDO+ versus IDO- murine DCs, we found a consistent and selective association of the IDO-competent phenotype with the down-modulation of the Tyrobp gene, encoding the adapter molecule DAP12. IFN-gamma-mediated down-modulation of this gene involved IFN consensus sequence binding protein (ICSBP), a transcription factor also known as IRF-8. While silencing of Tyrobp conferred IDO functional competence on IDO- DCs, silencing of Icsbp1 in IDO+ cells completely abolished IDO expression and function. In parallel, silencing of TYROBP conferred IDO competence on human IDO- DCs while silencing of IRF8 impaired IDO expression and activity in human IDO+ DCs. Therefore, the same small set of molecular switches controls IDO competence in murine and human DCs. Experiment Overall Design: Labeled cRNA extracted from a a total of 8 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 4 control samples included 2 replicates each of RNA extracted from cells incubated in medium for 4 and 16 hours. Treated samples included 2 replicates each of RNA extracted from cells incubated in IFN-gammas for 4 and 16 hours.
2007-09-11 | E-GEOD-3337 | biostudies-arrayexpress
Project description:All experiments are performed on human dendritic cells (DCs) differentiated in GM-CSF and IL-4 from CD14+ cells and bone marrow mesenchimal stem cells (MSCs). We found that MSCs impair active immune synapse formation and we evidenced at electron microscopy two types of contact between MSCs and DCs: gap and adherent junctions. In the same experiments we show that MSC contacts induce a reorganization of DC cytoskeleton by the formation of actin podosomes, structures typical of an immature, tolerogenic state of DCs. These results suggest that MSCs exert a tolerogenic effect on DCs by mechanism mediated by cell-cell contact. This induces DC cytoskeleton reorganization with formation of actin podosomes.
2010-12-31 | E-MTAB-286 | biostudies-arrayexpress
Project description:Tolerogenic dendritic cells (tol-DCs) offer a promising therapeutic potential for autoimmune diseases. Tol-DCs have been reported to inhibit immunogenic responses, yet little is known about the mechanisms controlling their tolerogenic status, as well as associated specific markers. Here we show that the anti-inflammatory TAM receptor tyrosine kinase MERTK, is highly expressed on clinical grade dexamethasone-induced human tol-DCs and mediates their tolerogenic effect. Neutralization of MERTK in allogenic mixed lymphocyte reactions as well as autologous DC-T cell cultures leads to increased T cell proliferation and IFN-g production. Additionally, we identify a previously unrecognized non-cell autonomous regulatory function of MERTK expressed on DCs. Recombinant Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK agonist Protein S (PROS1) expressed by T cells. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine pro-proliferative mechanism. Collectively, these results suggest that MERTK on tol-DCs directly inhibits T cell activation through the competition for PROS1 interaction with MERTK in the T cells. Targeting MERTK may provide an interesting approach to effectively increase or suppress tolerance for the purpose of immunotherapy. The complete database comprised the expression measurements of 54,675 genes for: immature (n=9), mature (n=7) and tolerogenic (n=8). Influence of treatment with dexamethasone (n=3) and LPS (n=2) are included.
2015-01-29 | E-GEOD-56017 | biostudies-arrayexpress
Project description:In this study, we focused on demonstrating the metabolic aspect of NCoR1 in the regulation of dendritic cells (DCs) functionality. We report that NCoR1 deficient tolerogenic DCs meet their anabolic requirements through enhanced glycolysis and OxPhos, supported by FAO-driven oxygen consumption. Furthermore, individual and dual inhibition of glycolysis through HIF-1α inhibitor (KC7F2) and fatty acid oxidation through CPT1 inhibitor (etomoxir) significantly impaired the secretion of tolerogenic cytokines. To validate the same at the global mRNA level we did bulk RNA-seq to determine the differentially expressed genes in control and NCoR1 KD 6h CpG activated DCs with and without inhibitor treatment.
2024-01-01 | E-MTAB-12066 | biostudies-arrayexpress