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C5aR+ dendritic cells fine-tune the Peyer’s patch microenvironment to induce antigen-specific CD8+ T cells

ABSTRACT: The mucosa is an ideal route for vaccination against pathogen infection, but the effective adjuvant capable of overcoming the tolerogenic dendritic cell (DC) environment is unavailable. We characterized type 2 conventional DCs and lysozyme-expressing monocyte-derived DCs (LysoDCs) of Peyer’s patches to identify the vaccination target cells through single-cell RNA sequencing. Based on functional analysis of the data, we suggest that C5aR+ LysoDCs and Co1 peptide, a C5aR ligand, as a target cell and an adjuvant, respectively, for mucosal vaccination. Co1-mediated stimulation of C5aR+ LysoDCs increased the level of reactive oxygen species, leading to CCL3-mediated chemotaxis and exogenous antigen cross-presentation, which elicited an antigen-specific CD8+ T cell response. In a SARS-CoV-2 vaccine model, Co1 peptide increased the frequency of antigen-specific polyfunctional CD8+ T cells in systemic as well as mucosal compartments. Collectively, LysoDC activation by Co1 peptide potentiates vaccination efficiency by constructing an immunostimulatory environment in the mucosal immune inductive site.

ORGANISM(S): Mus musculus

PROVIDER: GSE212701 | GEO | 2023/07/24

REPOSITORIES: GEO

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C5aR+ lysozyme-expressing dendritic cells (LysoDCs) comprise a unique cell population in the Peyer’s patch (PP) subepithelial dome (SED).

Project description:CD11chi cells can be subdivided into six different cell subsets:plasmacytoid DCs (pDCs), CD8a+ DCs, CD11b+ DCs, double-negative (DN) DCs, LysoDCs, and LysoMacs. Among these, LysoDC (CD4–) and LysoMacs (CD4+) are classified as CD11chiMHC class II+BST2intSIRPαhi lysozyme+ cells, depending on whether they express CD4. Here, we determine that C5aR expressed in LysoDC and LysoMacs. We used microarrays to determine the lineage of C5aR+ LysoDC and C5aR- LysoDC.

2021-04-12 | GSE138973 | GEO

Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients

Project description:Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients. We evaluate the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide (arm A) or electroporated with CEA-mRNA (arm B) to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. To evaluate immune responses, CEA-specific T cell reactivity is monitored in peripheral blood, resected abdominal lymph nodes, tumor tissue and biopsies of vaccination sites and post-treatment DTH skin tests. Patients are vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. In 2007 a side-study has been added (arm C), in which patients with stage III or high-risk stage II colorectal cancer that are amenable for standard adjuvant oxaliplatin/capecitabine therapy are vaccinated with CEApeptide-pulsed DCs. Also in this group, safety and immune responses in peripheral blood and the DTH-skin test are the primary endpoints. Results are compared with the results obtained in arm A.

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2016-05-29 | E-GEOD-72624 | biostudies-arrayexpress

Studies in a murine B16 melanoma model show that persistent antigen at vaccination sites induces CD8+ T cell sequestration, dysfunction and deletion

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2013-03-02 | E-GEOD-43929 | biostudies-arrayexpress

Choice of infection or immunity: microarrays analysis of the mechanism of CpG DNA enhancing the immune response on BMDCs pulsed with H9N2 AIV

Project description:Dendritic cells (DCs), professional antigen presenting cells, have demonstrated effective in controlling the initial of innate immune and enhancing immune response of vaccination, also proved that adjuvant CpG could improve the performance of immune system.Although exist many studies concerning the downstream response of DCs pulsed with CpG, rarely research gaze the interaction of DCs co-stimulated with CpG/H9N2 or CpG/inactivated H9N2 To explore the underlying molecular basis, we compared different stimulated mouse DCs with systemic approach microarrays The cultured mouse BMDCs were randomly divided into 6 groups (1: control DCs group, 2:CpG stimulated group, 3: H9N2 stimulated group, 4: CpG/H9N2 co-stimulated group, 5: inactivated H9N2 stimulated group, 6: CpG/inactivated H9N2 co-stimulated group). we used microarray to reveal striking transcriptome differences of different stimulated DCs.

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Gene expression data from Peyer's patch mononuclear phagocyte system

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Studies in a murine B16 melanoma model show that persistent antigen at vaccination sites induces CD8+ T cell sequestration, dysfunction and deletion

2013-03-02 | GSE43929 | GEO

Gene expression data from Peyer's patch mononuclear phagocyte system

Project description:Peyer’s patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution, ontogeny, lifespan, function and transcriptional profile of PP MPS. We show that monocytes give rise to macrophages and to lysozyme-expressing DC (LysoDC) which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures and, upon TLR7 stimulation, secrete IL-6 and TNF but no IL-10. However, unlike macrophages, LysoDC display a rapid renewal rate, strongly express genes of the MHCII presentation pathway and prime naïve helper T cells for IFNg production. Our results show that in PP, at steady state, monocytes generate both LysoDC and macrophages which display distinct features from their adjacent villus counterparts.

2015-02-03 | GSE65514 | GEO

Expression data from bone marrow derived DCs stimulated with different peptide-based nanovaccine formulations against L. infantum infection

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Analysis of DC vaccines used for phase II clinical trial in prostate carcinoma patients

Project description:Dendritic cell (DC)-based cancer vaccines are a promising immunotherapy against cancer. However, despite the vast number of clinical trials conducted so far, factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. Here, we performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258) and looked for correlates with clinical and immunological responses. DCs showing lower expression of tolerogenic gene signature induced strong antigen-specific immune response and slowing in Prostate Specific Antigen (PSA) velocity, a surrogate for clinical response. These DCs were also characterized by lower surface expression of CD14, secretion of IL-10 and MCP-1; and greater secretion of MDC. When combined, these four factors were able to remarkably discriminate DCs that were sufficiently potent to induce strong immunological response. In summary, we identified DC factors essential for the activation of immune responses associated with TARP vaccination in prostate cancer patients. This study highlights the importance of in-depth characterization of DC vaccines – and other cellular therapies, to understand the critical factors that hinder potency and potential efficacy in patients.

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