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Differences in the transcriptomic response of human adult and neonatal dendritic cell subsets to TLR7/8 stimulation

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67057 | GEO | 2015/06/30

SECONDARY ACCESSION(S): PRJNA278814

REPOSITORIES: GEO

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Differences in the transcriptomic response of human adult and neonatal dendritic cell subsets to TLR7/8 stimulation

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

Transcriptome profile of mouse lung dendritic cell subsets and macrophages.

Project description:Dendritic cell (DC) are critical initiators and regulators of immunity to pathogens, vaccines, tumors and tolerance to self. Mouse and human dendritic cells (DCs) are comprised of functionally specialized subsets, but precise interspecies correlation is currently incomplete and hampers the full translation of murine findings to human DC-based clinical therapies. In this study, we show that murine lung and gut lamina propria CD11b+ DC populations are comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64- DCs and contaminating CSF-1R-dependent CD24-CD64+ macrophages. CD11b+CD24+CD64- DCs are instrumental in inducing Th17 cell immune response in the steady state and upon Aspergillus fumigatus challenge. We also identified human CD1c+CD11b+ DCs as the functional homologue of mouse mucosal CD11b+ DCs. Our findings highlight the conservation of key immune functions across species and aid the translation of murine studies to human DC immunobiology. The data for the associated human studies have been stored within GSE35459. Gene Expression from total RNA from specific mouse dendritic cell subsets purified by FACS

2013-05-29 | E-GEOD-46680 | biostudies-arrayexpress

Proteome and phophoproteome analysis of distinct dendritic cell maturation states

Project description:Depending on their environment and their exposure to various factors, dendritic cells (DCs) exist in different activation and maturation states. The versatility of DCs allows them to shape the immune system towards an inflammatory or tolerant state depending on the antigens and the environment they encounter. In this study we aimed to provide a proteomic catalogue of differentially expressed and differentially phosphorylated proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed unlabeled shotgun proteomics and phosphoproteomics on cell fractions obtained from murine bone marrow DC cultures. The symbiont B. vulgatus stimulation was used to obtain semi-mature DCs, and the pathobiont E. coli stimulation was used to obtain mature DCs. For both shotgun proteome and phosphoproteome analysis two biological replicates consisting of 8 mice were used. Each biological replicate were run as 3 technical replicates.

2017-11-27 | PXD003738 | Pride

TAK1-dependent checkpoint in dendritic cell survival regulates immune homeostasis and function

Project description:Homeostatic control of dendritic cell (DC) survival is crucial for a productive adaptive immune response, but the molecular mechanism is not well defined. Moreover, how DCs influence homeostasis of the immune system under steady state remains unclear. Combining DC-specific and inducible deletion systems, we report here that the kinase TAK1 is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c+ cells diminished DC populations, especially the CD8+ and CD103+ DC subsets in the lymphoid and non-lymphoid organs, respectively. This was associated with increased apoptosis of DCs, whereas DC proliferation and differentiation from precursors appeared largely normal. In addition, acute deletion of TAK1 caused DC apoptosis, indicating a direct role of TAK1 in actively maintaining DC survival. TAK1 deficiency impaired activities of the pro-survival NF-kB and AKT pathways but upregulated expression of the pro-apoptotic molecule Bim. Under steady state, loss of TAK1 in DCs resulted in a myeloid proliferative disorder, and altered homeostasis of T cells. In response to antigen stimulation, TAK1-deficient DCs were impaired for T cell priming and regulatory T cell generation. Therefore, TAK1 orchestrates a pro-survival checkpoint in DCs that affects the homeostasis and function of the immune system RNA extracted from three replicate samples of wild-type and Map3k7 (TAK1) knockout dendritic cells was analyzed on Affymetrix gene expression arrays

2012-01-23 | E-GEOD-34417 | biostudies-arrayexpress

Transcriptome signature of WT and C3ar1-/-C5ar1-/- splenic DCs in response to CpG

Project description:Our group showed that DC-instrinsic C3ar1/C5ar1 signals are required for TLR-initiated DC maturation in vivo. To more broadly analyze how local complement signaling affects DC maturation process in response to TLR9 stimulation, WT or C3ar1-/-C5ar1-/- mice were stimulated with CpG (i.v. 100 micrograms) or vehicle control. 4hrs later, splenic CD11c+DCs were isolated and RNAs from the cells were purified for microarray analyses.

2017-04-29 | GSE98315 | GEO

Dendritic cell-derived IL-2 promotes apoptosis of terminally mature cells via a novel autocrine signaling pathway

Project description:Dendritic cells (DCs) are crucial for sensing pathogens and triggering immune response. GM-CSF myeloid dendritic cells (GM-DCs) secrete several cytokines including IL-2 upon activation by pathogen associated molecular pattern (PAMP) ligands. DC IL-2 has been shown to be important for innate and adaptive immune responses, however its importance in DC physiology has never been demonstrated. This is due to ambiguity in expression of the CD122 subunit of the IL-2 trimeric receptor complex crucial for signaling. We show here that autocrine IL-2 signaling is functional in GM-DCs in early time window of stimulation with PAMPs. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexs at the cell surface. Autocrine IL-2 signaling inhibits survival of PAMP matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest immune regulation by a novel autocrine signaling pathway that can potentially be exploited in DC immunotherapy. Microarray technology was used to understand the role of IL-2 signaling in DC. Microarray was performed to investigate the role of IL-2 signaling in DC physiology. Hence Wt or IL-2-/- BMDCs were either treated or not with curdlan for 6h and taken for microarray.

2015-05-21 | E-GEOD-58120 | biostudies-arrayexpress

TAK1-dependent checkpoint in dendritic cell survival regulates immune homeostasis and function

2012-01-23 | GSE34417 | GEO

PDL2+, PDL2- and LPS treated PDL2- WT bone-marrow derived murine DCs

Project description:Cultured BMDCs were purified by FACS sorting for PDL2 surface expression and stimulated with LPS at 100 ng/mL or left unstimulated. Microarray data was used to demonstrate gene expression differences between PDL2- and PDL2+ DC populations. Microarray data was also used to show that PDL2+ mature DCs were distinct from LPS treated DCs.

2013-09-17 | GSE50898 | GEO

Gene Expression Data in Human Monocyte-derived Dendritic Cell (MoDC) from Young and Aged Donors

Project description:Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs changes with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. We identified up and down-regulated gene expression changes in DC from aged donors compared to young donors.

2014-05-28 | GSE58015 | GEO

Gene expression by human splenic B-cell subsets

Project description:Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of naïve and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than naïve B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not naïve B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool. Keywords: cell type comparison Four subsets of human splenic B cells (naïve, IgM-memory, Ig isotype switched memory and plasma cells); sort-purified and analysed immediately ex vivo; performed in duplicate.

2008-12-30 | E-GEOD-13411 | biostudies-arrayexpress

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