Cytokine profile of mature WT bone marrow-derived dendritic cells and fascin1 knockout bone marrow-derived dendritic cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174285 | GEO | 2021/05/12
REPOSITORIES: GEO
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Project description:Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the SubSeries listed below.
2009-04-23 | GSE15784 | GEO
Project description:We performed RNA-seq analysis using primary murine bone marrow derived dendritic cells (BM-DCs) for recombinant articulatin B chain (rATB) treatment. We reported that rATB regulates immunological related genes in BM-DCs. rATB induces CD4 T cell type I driven and maturation genes in BM-DCs.
2023-12-31 | GSE189829 | GEO
Project description:Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the following subset Series: GSE15748: Gene expression in PLN vs. ILN or MLN in mice GSE15753: Gene expression in GLN versus PDLN in NOD mice Refer to individual Series
2009-04-23 | E-GEOD-15784 | biostudies-arrayexpress
Project description:Background : Poxviruses have been shown to be efficient vectors for the production of protective immune responses in host species but also in on host species. Myxoma virus belongs to poxviridae family. In order to evaluate the capacity of (MYXV) as a vaccine vector in ruminants, we invistigated its interactions with bone marrow-derived dendritic cells (BM-DC). DCs are the most potent antigen-presenting cells and play a crucial role during the priming and reactivation of antigen-specific immune responses . Following infection by a pathogen, the functional changes of DC are essential since priming and polarization of the immune response depend on these changes . Therefore a better understanding of the modifications in gene expression of proinflammatory cytokines, chemokines and stimulatory molecules expression may prove useful in predicting whether or not a vaccine vector will be effective. Moreover, it may help identifying modifications for improving its efficacy. Methodology/Principal Findings: We investigated in vitro the interactions between recombinant MYXV expressing GFP protein, SG33-GFP and ovine BM-DCs. To gain a global view of the gene remodelling induced by MYXV, we infected BM-DCs from three sheep with SG33-GFP at different multiplicity of infection (MOI) (0, 1, 3) during different time (0, 3, 8 hours). We measured the expression of 15K probes in BM-DCs after each kind of conditions with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. MYXV infection induces a strong reprogramming of the cells leading to the expression of pro-inflammatory cytokines and mobilisation of type I IFN pathways, cellular death and features associated with the activation of the adaptive immune response. Conclusion/Significance: Microarray profiling of a poxvirus-DC interaction help to delineate some interesting features of a vector candidate in ovine, and pave the way for additional improvements of a promising platform. Keywords : Myxoma virus ; bone marrow-derived dendritic cells ; transcriptome ; sheep; vaccine
2011-10-15 | GSE32656 | GEO
Project description:Francisella tularensis is a highly infective Gram-negative bacterium, also known as the causative agent of tularemia. The disease is characterized by the delayed onset of the adaptive immune response which provides time for the bacterial replication. As an intracellular pathogen, Francisella proliferates mainly in the cytosol of host phagocytes, which are linkers between the innate and the adaptive immunity. In particular, dendritic cells (DCs) are known to be the most effective antigen-presenting cells and thus they are crucial for the induction of the adaptive response. However, Francisella is able to invade and to proliferate inside DCs while avoiding their effective activation and maturation. The goal of this study was to map phosphoproteome changes in DCs infected by Francisella in order to reveal host signaling pathways involved in Francisella-DC interaction. The focus was laid on early intervals (<1 h p.i.) because of the ability of Francisella to escape in this time period from the phagosome to the cytosol where it establishes its replicative niche. For comparison, attenuated and in vivo-protective Francisella strain was used in parallel in experiments. DC phosphoproteome was analyzed by the means of shotgun LC-MS-based proteomics and relative changes were quantified by the stable isotope labeling method specially developed for primary bone marrow-derived DCs.
2017-10-26 | PXD005747 | Pride
Project description:Background : Poxviruses have been shown to be efficient vectors for the production of protective immune responses in host species but also in on host species. Myxoma virus belongs to poxviridae family. In order to evaluate the capacity of (MYXV) as a vaccine vector in ruminants, we invistigated its interactions with bone marrow-derived dendritic cells (BM-DC). DCs are the most potent antigen-presenting cells and play a crucial role during the priming and reactivation of antigen-specific immune responses . Following infection by a pathogen, the functional changes of DC are essential since priming and polarization of the immune response depend on these changes . Therefore a better understanding of the modifications in gene expression of proinflammatory cytokines, chemokines and stimulatory molecules expression may prove useful in predicting whether or not a vaccine vector will be effective. Moreover, it may help identifying modifications for improving its efficacy. Methodology/Principal Findings: We investigated in vitro the interactions between recombinant MYXV expressing GFP protein, SG33-GFP and ovine BM-DCs. To gain a global view of the gene remodelling induced by MYXV, we infected BM-DCs from three sheep with SG33-GFP at different multiplicity of infection (MOI) (0, 1, 3) during different time (0, 3, 8 hours). We measured the expression of 15K probes in BM-DCs after each kind of conditions with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. MYXV infection induces a strong reprogramming of the cells leading to the expression of pro-inflammatory cytokines and mobilisation of type I IFN pathways, cellular death and features associated with the activation of the adaptive immune response. Conclusion/Significance: Microarray profiling of a poxvirus-DC interaction help to delineate some interesting features of a vector candidate in ovine, and pave the way for additional improvements of a promising platform. Keywords : Myxoma virus ; bone marrow-derived dendritic cells ; transcriptome ; sheep; vaccine 9 samples: 3 time points and 3 replicates of MOI=1
2011-10-14 | E-GEOD-32656 | biostudies-arrayexpress
Project description:Following UV irradiation of skin, dendritic cells (DCs) differentiating from the bone marrow (BM) of mice have a reduced ability to prime new immune responses; their reduced immunogenicity is maintained for at least 16 weeks in UV-chimeric mice. We hypothesized that different metabolic states underpin changes in DC function. Compared with DCs from the BM of non-irradiated mice, DCs from the BM of UV-irradiated mice produced more lactate and utilized greater amounts of glucose, a profile that was supported by greater glycolytic flux when incubated in low-serum-containing medium. Responses to a mitochondrial stress test were similar suggesting that the DCs from the BM of UV-irradiated mice had not switched from a profile of oxidative phosphorylation, but were imprinted for greater glycolytic responses. After microarray profiling, RT-qPCR confirmation and Ingenuity pathway analysis, greater expression of the enzyme, 3-hydroxyanthranilate 3,4-dioxygenase, was identified as a potential contributor to increased glycolysis by BM-differentiated DCs. This enzyme provides the final step of the biosynthetic pathway from tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide (NAD), and may provide a mechanism to ensure sufficient NAD is available to support enhanced glycolysis. Increased lactate production was also measured for DCs from the BM of 16-week engrafted UV-chimeric mice and suggests long-lasting imprinting of progenitor cells for altered immunometabolism in their progeny cells. This study provides evidence of changes to metabolic states that associate with altered DC function.
2015-10-30 | GSE74468 | GEO
Project description:As an essential cellular component of the bone marrow (BM) microenvironment mesenchymal stromal cells (MSC) play a pivotal role for the physiological regulation of hematopoiesis, in particular through the secretion of cytokines and chemokines. Mass spectrometry (MS) facilitates the identification and quantification of a large amount of secreted proteins (secretome), but can be hampered by the false-positive identification of contaminating proteins released from dead cells or derived from cell medium. To reduce the likelihood of contaminations we applied an approach combining secretome and proteome analysis to characterize the physiological secretome of BM derived human MSC. Our analysis revealed a secretome consisting of 315 proteins. Pathway analyses of these proteins revealed a high abundance of proteins related to cell growth and/or maintenance, signal transduction and cell communication thereby representing key biological functions of BM derived MSC on protein level. Within the MSC secretome we identified several cytokines and growth factors such as VEGFC, TGF-β1, TGF-β2 and GDF6 which are known to be involved in the physiological regulation of hematopoiesis. By comparing the peptide patterns of secretomes and cell lysates 17 proteins were identified as candidates for proteolytic processing. Taken together, our combined MS work-flow reduced the likelihood of contaminations and enabled us to carve out a specific overview about the composition of the secretome from human BM derived MSC. This methodological approach and the specific secretome signature of BM derived MSC may serve as basis foffuture comparative analyses of the interplay of MSC and HSPC in patients with hematological malignancies.
2019-02-12 | PXD011643 | Pride
Project description:Francisella tularensis is a highly infective Gram-negative bacterium, also known as the causative agent of tularemia. The disease is characterized by the delayed onset of the adaptive immune response which provides time for the bacterial replication. As an intracellular pathogen, Francisella proliferates mainly in the cytosol of host phagocytes, which are linkers between the innate and the adaptive immunity. In particular, dendritic cells (DCs) are known to be the most effective antigen-presenting cells and thus they are crucial for the induction of the adaptive response. However, Francisella is able to invade and to proliferate inside DCs while avoiding their effective activation and maturation. The uploaded dataset relates to phosphoproteome analysis of DCs infected by virulent and attenuated Francisella strains (dataset identifier PXD005747) and provides data of DC proteome changes at 60 min p.i.
2017-10-26 | PXD006759 | Pride
Project description:In this study, we aimed to determine the role of EVs derived from Lm-infected DCs in the innate response, and the potential role of HDAC6 in DEV loading under these conditions. Our results show that Lm infection induced an elevated production of DEVs. Lm infection also altered protein sorting. Interestingly, HDAC6 deletion altered DEV protein sorting, although it did not affect acetylation of DEV-loaded proteins. However, protein ubiquitination was severely altered. Here, we show that the protein content of dendritic cells (DCs) and their secreted EVs (DEVs) vary dramatically during Lm infection. The proteomic profiles of DCs and DEV differ depending on whether HDAC6 is expressed or not.
2022-08-30 | PXD033998 | Pride