This study provides the dectin-1 and NFAT responsive genes for 2h and 4h of curdlan treatment.
NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
Specimen part
View SamplesDendritic 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.
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Specimen part
View SamplesOur study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)). Overall design: Lungs were harvested from neutrophil-depleted (antibody or DT) or non-depleted mice, in normal light-controlled mouse facility (ZT4) or 12h inverted light cabinets (ZT16). Experiments were carried out over 3 batches (July 2017, September 2017, and April 2018), with 3 or 4 mice per group. Antibody-depleted and non-depleted mice were tested for the July 2017 and September 2017 batches, whereas DT-depleted mice were tested only in April 2018.
Neutrophils instruct homeostatic and pathological states in naive tissues.
Specimen part, Treatment, Subject
View SamplesWe explored the hypothesis that Serotonin (5HT) receptor signaling, that can be enhanced with 5HT transporter blockade with Fluoxetine (Fluox), in the aortic valve may vary based upon the biomechanical activity of the aortic valve leaflet.
Aortic valve cyclic stretch causes increased remodeling activity and enhanced serotonin receptor responsiveness.
Specimen part, Disease, Treatment
View SamplesPurpose: In our study, we identified a heterogeneity among bone marrow (BM) Ly6Chi monocytes, which can be subdivided the expression of CXCR4. In order to understand the development of BM monocytes, the goal of this experiment is to compare the transcriptome of these 2 BM Ly6Chi monocyte subsets to those of the common monocyte progenitor (cMoP) and Ly6Clo monocytes. Overall design: 4 BM monocyte subsets (cMoP, Ly6ChiCXCR4hi, Ly6ChiCXCR4lo and Ly6Clo) from 3 different mice were sorted using a BD Aria III. Total RNA was extracted, converted to cDNA and run through deep sequencing using Illumina HiSeq 2500
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.
Age, Specimen part, Cell line, Subject
View SamplesPurpose: We have identified a new compound (1C8) that inhibits HIV-1 replication and that displays very low cellular toxicity. Here, we assess the molecular mechanisms of action of 1C8. Following transcription of the HIV-1 genome, its primary transcript is processed to produce dozens of distinct mRNAs through the alternative use of splice sites. Results: 1C8 decreases the activity of SRSF10, a cellular protein that controls the selection of splice sites in HIV-1 transcripts. 1C8 decreases the phosphorylation of SRSF10, and this change is associated with alterations in the interaction of SRSF10 with HIV-1 transcripts and factors that control splice site selection. Thus, 1C8 represents a novel compound with properties that are potentially useful for treating HIV-1 infection. Overall design: Examination of RNA-seq to investigate alternative splicing changes between control and 4 different concentrations of a drug that 1C8. 4 replicates were sequenced for each condition.
Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication.
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View SamplesMacrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within tissue parenchyma remain poorly defined. Here, we studied IMs from murine lung, fat, heart and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming. Overall design: Mouse Lung Interstitial Macrophages single cell mRNA profiles
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.
Specimen part, Subject
View SamplesMacrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within tissue parenchyma remain poorly defined. Here, we studied IMs from murine lung, fat, heart and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming. Overall design: FACS sorted cells from several animals
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.
Specimen part, Subject
View SamplesThe gene expression profile of TAMs microbead isolated from freshly obtained human GISTs were compared in tumors that were untreated, responding to imatinib (sensitive), or resistant to imatinib (resistant)
KIT oncogene inhibition drives intratumoral macrophage M2 polarization.
Specimen part
View SamplesWe used RNA-seq as a method of next generation sequencing (NGS) to identify RIPK1 dependent inflammatory mediators and pathways in LPS injected mice. Overall design: Mice were divided intro 3 groups - control (n=2), LPS (n=2) and LPS/Nec-1 (n=2). BM cells were isolated by FACS as described for qPCR analysis. Total RNAs were isolated using Qiagen RNeasy kit according to the manufacturer's protocol
RIPK1 and RIPK3 Kinases Promote Cell-Death-Independent Inflammation by Toll-like Receptor 4.
Specimen part, Cell line, Treatment, Subject
View Samples