Human Dendritic Cell Subtype Gene Arrays
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE11943 | GEO | 2008/07/01
SECONDARY ACCESSION(S): PRJNA105797
REPOSITORIES: GEO
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Project description:Among the dendritic cell (DC) subsets, plasmacytoid DCâs are thought to be important in both generating antiviral and antitumor responses. These cells may be useful in developing dendritic cell-based tumor vaccines, however, the rarity of these cells in the peripheral blood have hampered attempts to understand their biology. To provide better insight into the biology of plasmacytoid DCs, we isolated these cells from the peripheral blood of healthy donors in order to further characterize their gene expression. Using gene array technology we compared the genetic profiles of these cells to those of CD14+ monocytes isolated from the same donors and found several immune related genes upregulated in this cell population. Understanding the genetic profiles of this dendritic cell subtype as well as others such as the BDCA-1 expressing myeloid DCs may enable us to manipulate these cells ex-vivo to generate enhanced DC-based tumor vaccines inducing more robust antitumor responses. Experiment Overall Design: 4 replicates of BDCA cells and CD14 cells
2008-10-21 | E-GEOD-11943 | biostudies-arrayexpress
Project description:Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a new strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.
2023-07-22 | GSE238016 | GEO
Project description:Although promising, dendritic cell (DC) vaccines still provide limited clinical benefits, mainly due to the immunosuppressive tumor microenvironment (TME) and the lack of tumor-associated antigens (TAAs). Oncolytic viruses are considered to be an ideal strategy to overcome immunosuppression and expose TAAs, therefore they may work synergistically with DC vaccines. In this study, we demonstrated that oncolytic virus M1 (OVM) can enhance the antitumor effects of DC vaccine in a variety of syngeneic tumor mouse models by increasing the infiltration of CD8+ effector T cells in the TME. Mechanically, we identified that tumor cells offset the function of DC vaccines through the myeloid immune checkpoint SIRPα-CD47, while OVM can downregulate the expression of SIRPα and CD47 in DCs and tumor cells, respectively. Based on the fact that OVM upregulates the expression of PD-L1 in DCs, PD-L1 blockade was introduced with the combination of DC vaccines and OVM, resulting in a further potentiation of antitumor activity. Overall, we revealed that OVM can strengthen the antitumor efficacy of DC vaccines by targeting the immune checkpoint SIRPα-CD47 axis, which exerts dominant immunosuppressive effects on DC vaccines.
2023-09-01 | GSE222080 | GEO
Project description:An unexpected BDCA-2+CD123+CD1a+ dendritic cell (DC) subset comprised a major DC population in acute human sterile skin inflammation. Single-cell RNAseq showed these to be activated DC able to express markers normally associated with plasmacytoid DC, prompting a re-evaluation of previous studies.
2019-12-01 | E-MTAB-8498 | biostudies-arrayexpress
Project description:Cancer vaccines utilizing naturally circulating dendritic cell (DC) subsets, such as plasmacutoid DCs (pDCs) and type 2 convential DCs (cDC2s), have demonstrated their potential as a therapy. For melanoma in recent clinical trials. These DC vaccines aim to. human. DC subsets on the. T cell transcriptional program, which. forms the. molecular. basis. of an. antitumor. T cell response, is. poorly understood. In. this study, we investigated the eraly gene expressionsignature of CD8+ T. cells following. stimulation by pDCs or cDC2s. in. a culture system that mimics. the. current protocol of primary DC-based cancer vaccines. Our results demonstrate that pDCs and cDC2s induce a remarkably similar transcriptomic profile in CD8_ T cells, which. is tailored for increased effector function, survival and sensitivity. towards secondary signals. Nonetheless, differences between pDC- and cDC2-induced T cell gene expression signatures encompass genes with a role in proliferation, cytolytic capacity and differentiation. Combining both DC subsets results in a T cell. transcriptomic program that. is very. similar to. the program induced by. pDCs alone. The results suggest that the. choice of DC subsets for use in cancer vaccines impacts the induced antitumor CD8+ T cell response.
2020-04-01 | GSE142631 | GEO
Project description:We exploited label-free quantitative mass spectrometry to compare primary human blood Dendritic cells (DCs) subsets protein expression to identify new markers. Subsets distinguished are: Plasmacytoid DCs (pDC) and BDCA3+ and CD1c+ myeloid DCs and CD16+ monocytes. The dendritic cells were analyzed by LC-MS/MS and processed by MaxQuant for identification and LFQ quantification.
2016-09-27 | PXD004678 | Pride
Project description:Previous studies have shown that purified dendritic cells (DCs) have cell-intrinsic, age-dependent differences in their response to TLR stimulation. To delineate which aspects of the age-dependent difference in innate immunity are cell intrinsic vs extrinsic, we searched for global differences to TLR7/8 stimulation in purified adult vs neonatal DC populations. We hypothesize that very few selected cell intrinsic differences in gene expression of key immune genes between these 2 age groups exist, and the bulk would be cell extrinsic differences. The results show that there are age-dependent differences in expression of several key genes involved in the immune response at baseline already. Upon stimulation, we identified a substantially larger fraction of age-dependent differentially expressed genes in conventional than plasmacytoid DCs. Bioinformatics analyses indicate that important immune pathways were significantly differentially expressed in DC subsets between the 2 age groups. Total RNA was isolated from purified human conventional and plasmacytoid dendritic cells from 6 adult and 6 cord blood donors that were stimulated with 3M-003 at a final concentration of 5 uM for 1 and 6 hr.
2015-06-30 | E-GEOD-67057 | biostudies-arrayexpress
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines. 5 donors; 88 samples; duplicate technical replicates for the medium control for each donor for the BDCA1+ mDC population; single medium control for each donor for the BDCA3+ mDC population (15 total medium controls).
2014-10-22 | E-GEOD-56744 | biostudies-arrayexpress
Project description:Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major 'inflammatory' dermal DC population in psoriasis vulgaris and CD1c+ DCs as the 'resident' cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis. Shave biopsies were cultured overnight in dispase to remove the epidermis. Dermis was cultured for 36-48 hours to obtain dermal single cell suspensions. These cells were stained with HLA-DR, CD11c, BDCA-1 (DCs) and FACS-sorted into HLA-DR+11c+BDCA-1+, HLA-DR+11c+BDCA-1- populations into Trizol. RNA was extracted and processed for microarray. 2 dependent groups.
2010-06-08 | E-GEOD-20264 | biostudies-arrayexpress
Project description:The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. Dendritic cells (DC) were purified from the blood of healthy human donors. Each replicate comes from a different donor. There are 6 freshly purified samples (Control_0h), 4 DC samples cultured during 6h with no additional stimulus than the medium (Control_6h), 5 samples cultured during 6h with recombinant TSLP (Thymic Stromal Lymphopoietin at 20 ng/uL) (TSLP_6h) and 3 samples cultured during 6h with recombinant TNF (Tumor necrosis factor at 20 ng/mL) (TNF_6h).
2014-08-01 | E-GEOD-59237 | biostudies-arrayexpress