Project description:High-dimensional approaches have revealed emerging heterogeneity within dendritic cells (DC), including a population of transitional DC (tDC) present in mouse and human. However, tDC origin and relationship to other DC subsets are not fully understood because their phenotype partially overlaps with previous definitions of conventional DC precursors (pre-cDC). Here, we show that tDC are distinct from other well-characterized DC and pre-cDC. By combining single-cell transcriptomics, high-dimensional immunophenotyping, lineage tracing and adoptive transfer experiments, we demonstrate that murine tDC originate from bone marrow progenitors shared with plasmacytoid DC (pDC) that are distinct from CD115-expressing conventional DC progenitors. In the periphery, tDC contribute to the pool of Esam+ type 2 DC (DC2), and these tDC-derived DC2 harbor pDC-related developmental features. tDC have lower turnover than pre-cDC2, capture antigen, respond to stimuli, and potently antigen-specific naïve T cells, all characteristics of differentiated DC. Different from pDC, viral sensing by tDC results in IL-1β secretion and fatal immune pathology in a model of murine coronavirus. Our findings suggest that tDC are a distinct pDC-related lineage with a DC2 differentiation potential and unique pro-inflammatory function during viral infections. The objective of this experiment was to evaulate the transcriptional changes in various dendritic cell subpopulations
Project description:Analysis of FACS-sorted conventional dendritic cell type 1 (cDC1) subpopulation in mediastinal lymph nodes (mLNs) from mice with vacuolar protein sorting 33B (Vps33B) specific deletion in DCs in response to house dust mite (HDM). Our results provide insight into the role of Vps33B in regulating the function of cDC1s upon HDM stimulation.
Project description:Dendritic cells (DCs), the primary antigen-presenting cells, have traditionally been identified by CD103 molecules in rats, whereas mouse and human DCs are identified by CD11c molecules. However, this history does not preclude the existence of CD103- DCs in rats. To explore this possibility, we examined MHCII+ cells in rat spleen and thymus, identifying a novel population of CD103-MHCII+CD45R-CD172a+ cells. These cells are negative for CD103 and B cell marker CD45R, but positive for the type-2 conventional DC (cDC2) marker CD172a. Transcriptomic analyses revealed that they represent a subpopulation of cDC2.
Project description:Interventions: Dendritic cell-based cancer vaccination;Cancer, dendritic cell, vaccination
Primary outcome(s): Safety (adverse reactions, severe adverse events)
Study Design: single arm study,open(masking not used),uncontrolled control,single assignment
Project description:Newly Found Rat CD103− Dendritic Cells Represent a Highly Immunogenic Subpopulation of Type-2 Conventional Dendritic Cells, Corresponding to Known Dendritic Cell Subsets in Mice and Humans
Project description:dendritic cells = improtant APC -different subtypes characterized by surface markers by FACS -combination of FACS and LC-MS powerful tool, especially for low cell numbers -direct sorting of cells into SP3-compatible lysis buffer -new protocol without washing steps after sort and before protein digestion
Project description:A distinct highly invasive subpopulation was identified in breast cancer cell lines. The molecular characteristics of these cells was investigated, revealing a set of genes whose high expression confers the ability to invade. Total RNA isolated from the invasive subpopulation from 2 cells lines was compared to total RNA isolated from 2 noninvasive populations.
Project description:Single arm Phase I/II multicentric open labeled, with translational sub-study, of avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients..