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GSE59896
Mus musculus
15 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study provides the dectin-1 and NFAT responsive genes for 2h and 4h of curdlan treatment.
Publication Title
NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
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.
Publication Title
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Characterization of colon CD11chigh/MHCII+ myeloid cell subsets
Publication Title
Intestinal CD103(+)CD11b(-) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, -glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.
Publication Title
Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Monocytes, neutrophils and tissue resident macropahges of colon lamina propia are compared to their intratumoral counterparts found in colon adenomas Overall design: Different myeloid subpopulations were isolated from healthy colon lamina propria and colon adenomas, sorted by flow cytometry and processed for RNA.
Publication Title
The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
MHC class I-related molecule MR1 presents riboflavin-derived microbial metabolites and folate-derivatives to mucosal-associated invariant T cells, but it is unknown whether MR1 can bind alternative antigens that stimulate other T cell lineages. Here we report that human T cells displaying diverse TCR-a and ß chains recognize MR1-expressing cells in the absence of microbial ligands and respond to recombinant MR1 molecules loaded with antigens extracted from stimulatory targets. Transcriptome analysis revealed functional heterogeneity of MR1-reactive T cells (MR1T cells), which displayed differential expression of various transcription factors regulating T cell polarization, proliferation and apoptosis. Accordingly, MR1T cells displayed multiple profiles of chemokine receptor expression and secreted variable combinations of cytokines and growth factors, suggesting a diversity of immunological roles across numerous tissues. Functionally, MR1T cells were capable of inducing dendritic cell maturation and stimulating anti-microbial responses in intestinal epithelial cells. These data demonstrate that MR1 presents endogenous antigens to a novel population of functionally diverse human T cells. Overall design: mRNA profiles of two representative MR1T cell clones in resting (not exposed to antigen) and activated (stimulated with A375-MR1 antigen target cells and activated) states
Publication Title
Functionally diverse human T cells recognize non-microbial antigens presented by MR1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Complex regulatory mechanisms control continuous maintenance of myeloid progenitors and renewal of differentiated cells. Transcription factors play a important role in these processes. Here we report that the activation the calcineurin-NFAT signaling pathway inhibit the proliferation of myeloid granulocyte-monocyte progenitor (GMP). Myeloid progenitor subtypes possessed different susceptibilities to Ca2+ flux induction and consequently differential engagement of the calcineurin-NFAT pathway. This study show that inhibition of the calcineurin-NFAT pathway enhanced proliferation of GMPs both in vivo and in vitro. The calcineurin-NFAT signaling in GMPs is initiated through Flt3-L. The inhibition of the calcineurin-NFAT pathway altered the expression of the cell cycle regulation genes CDK4, CDK6, and CDKN1A, thus enabling faster cell cycle progression. The extensive use of NFAT inhibitors in the clinic should take into account that, in addition to the immunosuppression role in lymphoid cells, these NFAT inhibitors also affect the maintenance of the myeloid compartment.
Publication Title
Calcium and calcineurin-NFAT signaling regulate granulocyte-monocyte progenitor cell cycle via Flt3-L.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 122 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed RNA-Seq transcriptome profiling on 29 immune cell types consituting peripheral blood mononuclear cells (PBMCs) sorted from 4 Singaporean-Chinese individuals (S4 cohort). We also performed RNA-Seq and microarray transcriptome profiling of PBMCs from an extended cohort of 13 individuals (S13 cohort). The data was used first to characterize the transcriptomic signatures and relationships among the 29 immune cell types. Then we explored the difference in mRNA composition in terms of transcripts proportions and abundance. Lastly, we performed deep deconvolution for both microarray and RNA-Seq technologies. Overall design: Total RNA of 29 immune cell types (from 4 individuals) and peripheral blood mononuclear cells (PBMCs, from 13 individuals) was extracted for gene expression profiling. The 13 PBMCs samples were processed with both microarray and RNA-Seq platforms.
Publication Title
RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Following combined stimulation through Toll-like receptor (TLR)-9 and the B-cell receptor (BCR), human B cells were sorted based on IL-10 expression.
Publication Title
Human regulatory B cells combine phenotypic and genetic hallmarks with a distinct differentiation fate.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We analysed by bulk RNA seq the impact of the depletion of EZH2 on Langerhans cells Overall design: Langerhans cell from the skin of WT and EZH2 KO mice have been sorted and their transcriptomic profile has been analysed by bulk RNA seq
Publication Title
Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples