Similar Datasets
Project description:Cross-presentation by dendritic cells is limited by non-canonical autophagy.
| PRJNA553189 | ENA
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity. Comparison of murine mannose receptor negative versus mannose receptor positive bone marrow-derived DCs
2010-05-08 | E-GEOD-15616 | biostudies-arrayexpress
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity.
2009-06-19 | GSE15616 | GEO
Project description:Cross-presentation of tumor antigens by dendritic cells (DCs) is crucial to prime and (re-) stimulate CD8+ T cells. This process is important in initiating and maintaining an anti-tumor response. Here, we show that tumor presence of conventional type 1 DCs (cDC1), a subtype that excels in cross-presentation, correlates with response to neoadjuvant immune checkpoint blockade (ICB) in melanoma. This led us to hypothesize that patients failing to respond to ICB could benefit from enhanced cross-presentation of tumor antigens. We therefore established a cross-presentation assay to screen over 5,500 compounds for enhancers of DC cross-presentation using induced T cell proliferation as readout. We identified 145 enhancers, including AZD5582, an antagonist of inhibitor of apoptosis proteins (IAPs) cIAP1, cIAP2 and XIAP. AZD5582 treatment led to DC activation of the non-canonical nuclear factor kappa B (NF-kB) pathway, enhanced antigen import from endolysosomes into the cytosol and increased expression of genes involved in cross-presentation. Furthermore, it upregulated expression of CD80, CD86, MHC class II, CD70 and secretion of TNF by DCs. This enhanced DC activation and maturation program was observed also in tumor-bearing mice upon AZD5582 treatment, culminating into an increased frequency of systemic tumor antigen-specific CD8+ T cells. Our results merit further exploration of AZD5582 to increase antigen cross-presentation for improving the clinical benefit of ICB in unfavorable patients.
2023-03-23 | GSE217050 | GEO
Project description:Cross-presentation of tumor antigens by dendritic cells (DCs) is crucial to prime and (re-) stimulate CD8+ T cells. This process is important in initiating and maintaining an anti-tumor response. Here, we show that tumor presence of conventional type 1 DCs (cDC1), a subtype that excels in cross-presentation, correlates with response to neoadjuvant immune checkpoint blockade (ICB) in melanoma. This led us to hypothesize that patients failing to respond to ICB could benefit from enhanced cross-presentation of tumor antigens. We therefore established a cross-presentation assay to screen over 5,500 compounds for enhancers of DC cross-presentation using induced T cell proliferation as readout. We identified 145 enhancers, including AZD5582, an antagonist of inhibitor of apoptosis proteins (IAPs) cIAP1, cIAP2 and XIAP. AZD5582 treatment led to DC activation of the non-canonical nuclear factor kappa B (NF-kB) pathway, enhanced antigen import from endolysosomes into the cytosol and increased expression of genes involved in cross-presentation. Furthermore, it upregulated expression of CD80, CD86, MHC class II, CD70 and secretion of TNF by DCs. This enhanced DC activation and maturation program was observed also in tumor-bearing mice upon AZD5582 treatment, culminating into an increased frequency of systemic tumor antigen-specific CD8+ T cells. Our results merit further exploration of AZD5582 to increase antigen cross-presentation for improving the clinical benefit of ICB in unfavorable patients.
2023-03-23 | GSE217048 | GEO
Project description:Dendritic cells are the initiators of the adaptive immune response, therefore its gene expression allow us to predict the responses to vaccination. We used bone marrow derived dendritic cells (BMDC) to analyze the gene expression that result from the exposure to adjuvants. We use model antigen OVA and cyclic di-AMP (CDA) as an adjuvant in order to characterize the genes involved in the activation of dendritic cells by CDA alone or when the antigen is present. Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8+ cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation
2017-07-15 | GSE101466 | GEO
Project description:CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of cross-presentation to the induction of anti-viral cytotoxic T cells remains debated. Here, we used a recombinant influenza virus expressing a NS1-GFP reporter gene to visualize the route of antigen presentation by lung dendritic cells (DC) upon viral infection in vivo. We found that lung CD103+ DC are the only subset to carry intact GFP protein to the draining lymph nodes. Strikingly, lung migratory CD103+ DC are not productively infected by influenza virus and thus induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also show that CD103+ DC resistance to infection correlates with an increased antiviral state in these cells that is dependent on the expression of IFN receptor alpha. In conclusion, these results establish that efficient cross-priming by migratory lung DC is coupled to the acquisition of an anti-viral status, which is dependent on type I IFN signaling pathway. mRNA profiles were generated by deep-sequencing in Illumina HiSeq2000 from alveolar macrophages and CD103+ dendritic cells from lungs of untreated and flu-treated mice
2013-06-19 | E-GEOD-38838 | biostudies-arrayexpress
Project description:Here we used a newly identified Sec61 blocker, mycolactone, to analyze Sec61 contribution to antigen cross presentation, ERAD and transport of internalized antigens into the cytosol in dendritic cells. Shotgun proteomics were used to asses the broad-ranging effects of Sec61 blockade on dendritic cells and its effect on critical proteins required for antigen presentation and ERAD.
2017-07-11 | PXD006103 | Pride
Project description:Dendritic cells (DC) play central roles in coordinating appropriate immune responses to pathogens. In the present study, the genes regulated by NFkB activators, RelB and cRel, in PAMP-induced bone marrow dendritic cells (BMDCs) activation was examined. Total RNA extracted from WT, relb-/-, crel-/-relb-/- bone marrow derived dendritic cells (BMDCs) were subjected to stimulation with CpG or Pam3CSK4.
2012-10-01 | E-GEOD-34990 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo we specifically targeted antigens to the two major subsets of DCs using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on MHC class II. This difference in antigen processing is intrinsic to the DC subsets and associated with increased expression of proteins associated with MHC processing. Experiment Overall Design: This study includes data from cell sort purified dendritic cells, B cells and CD4 and CD8 T cells. The genearray was performed to identify the transmembrane molecule recognized by the antibody 33D1. The antibody 33D1 binds specifically to CD8-CD11cHigh DCs in the spleen. Therfore the data set was reduced in this way that all molecules that are expressed either in CD8=CD11cHigh DCs, B cells and T cells were diminished of the CD8+CD11cHigh DC data set. This Genearray was also used to analyze MHC class I and MHC class II associated moelcules as the DC subsets differ in the antigen presentation. Each Series consists of 3 individuall samples
2008-06-14 | E-GEOD-6259 | biostudies-arrayexpress