The effect of TIM-3 stimulation on the gene expression profile of IgE/antigen-activated mouse mast cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE14438 | GEO | 2009/10/01
SECONDARY ACCESSION(S): PRJNA111775
REPOSITORIES: GEO
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Project description:TIM-3 is known to be expressed on dendritic cells, monocytes, melanoma cells, mast cells and on activated Th1 cells. In activated Th1 cells, stimulating TIM-3 by one of its ligands, galectin-9, leads to apoptosis and thus it plays a central role in terminating Th1-type immune responses. Interestingly, in IgE/antigen-activated mast cells TIM-3 enhances the production of IL-13 and IL-4. To get a more complete picture about the gene expression changes induced by TIM-3 in mast cells, in vitro differentiated mouse immature mast cells were stimulated by an agonist anti-TIM-3 antibody and IgE-sensitized mouse immature mast cells were activated by antigen and an agonist anti-TIM-3 antibody for 2 or 16 hours (overnight). Experiment Overall Design: Bone marrow cells were differentiated in RPMI + 10% FCS + 5 ng/ml mouse IL-3 + 40 ng/ml mouse SCF for >4 weeks. The purity of the cell cultures was >90% at this time point (FcERIa+/c-kit+ cells). These in vitro-differentiated immature mast cells were then treated by either control goat IgG or an agonist anti-mouse TIM-3 antibody (RnD Systems, 15 ug/ml for 2 or 16 hours). For the IgE/antigen-activated mouse mast cells, these in vitro-differentiated immature mast cells were sensitized by 5 ug/ml anti-DNP IgE (Sigma) for 1 hour and then treated with 100 ng/ml DNP-HSA (antigen, Sigma) and either control goat IgG or an agonist anti-mouse TIM-3 antibody (RnD Systems, 15 ug/ml) for 2 or 16 hours. The anti-TIM-3 samples were labeled by Cy5 and they were compared to the Cy3-labeled, goat IgG controls in a dual-color, paired experimental setup. The Agilent Whole Mouse Genome 4x44K expression microarray kit and Dual-Color Protocol version 5.5 were used in the experiments.
2009-10-15 | E-GEOD-14438 | biostudies-arrayexpress
Project description:The aim of this study was to investigate microRNA expression pattern and its functional relevance on the commitment toward mucosal differentiation and on IgE-mediated activation of mast cells. To identify microRNA genes the expression of which change during the differentiation and activation of murine primary mast cells in vitro, the putative committed progenitors (c-kit+ cells isolated on day 6 from differentiating cultures), immature mast cells (BMMC), mucosal-type mast cells (MMC), and IgE-activated mast cells were compared by Agilent microRNA array. RNA was isolated by miRNeasy (Qiagen) from: 1) c-kit+ cells, isolated from differentiating cultures (in the presence of IL3 and SCF) derived from the bone marrow using MACS column purification, 2) immature BMMCs obtained by cultivation of bone marrow cells in the presence of IL3 and SCF for 4 weeks, 3) mucosal-type mast cells by additional differentiation of immature BMMCs for 5 days by supplementation of IL9 and TGFbeta, and 4) activated mast cells by presensitization with anti-DNP IgE followed by IgE-crosslinking by DNP-antigen challenge for 2 hours. Agilent microRNA microarray was run on these experimental groups. Four biological replicates were included in every experimental group.
2011-01-01 | E-GEOD-24321 | biostudies-arrayexpress
Project description:The aim of this study was to investigate microRNA expression pattern and its functional relevance on the commitment toward mucosal differentiation and on IgE-mediated activation of mast cells. To identify microRNA genes the expression of which change during the differentiation and activation of murine primary mast cells in vitro, the putative committed progenitors (c-kit+ cells isolated on day 6 from differentiating cultures), immature mast cells (BMMC), mucosal-type mast cells (MMC), and IgE-activated mast cells were compared by Agilent microRNA array.
2011-01-01 | GSE24321 | GEO
Project description:The effect of TIM-3 stimulation on the gene expression profile of IgE/antigen-activated mouse mast cells
| PRJNA111775 | ENA
Project description:Mast cells produce a large amount of several chemokines after cross-linking of FceRI and participate in the pathogenesis of allergic diseases. The objective of this study was to comprehensively investigate FceRI-mediated chemokine induction in human mast cells and the effect of a corticosteroid (dexamethasone) and a calcineurin inhibitor (FK506). Human peripheral blood-derived mast cells were stimulated with anti-IgE antibody in the presence of dexamethasone or FK506. Expression of eight chemokines was significantly induced in mast cells by anti-IgE stimulation. Induction of CCL2, CCL7, CXCL3 and CXCL8 by anti-IgE was significantly inhibited by dexamethasone. In contrast, induction of CCL1, CCL3, CCL4 and CCL18 was significantly inhibited by FK506. Combination of dexamethasone and FK506 suppressed production of all chemokines by anti-IgE stimulation. These results suggest that corticosteroids and calcineurin inhibitors inhibit expression of distinct subsets of chemokines and a combination of these drugs almost completely suppresses the induction of all chemokine genes in human mast cells in response to FceRI-dependent stimulation. Human peripheral blood-derived mast cells were stimulated with anti-IgE antibody in the presence of dexamethasone or FK506. Gene expression profiles were evaluated using GeneChip Human Genome U133 plus 2.0 probe arrays (Affymetrix).
2009-03-12 | E-GEOD-15174 | biostudies-arrayexpress
Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.
2012-05-01 | E-GEOD-35332 | biostudies-arrayexpress
Project description:The high-affinity Fc receptor for IgE, mainly present on mast cells and basophils, plays a crucial role in the development of allergic diseases. Monomeric IgE binding to receptor regulates mast cell survival, differentiation, and maturation. However, the underlying molecular mechanism remains unclear. Here we demonstrate that, prior to IgE binding, IgE receptor mostly exists as a homo-dimer on human mast cell membrane. The structure of human IgE receptor confirms the dimeric organization. Cholesterol-like molecules embedded within the transmembrane domain may stabilize the dimeric assembly. Upon IgE binding, the dimeric IgE receptor dissociates into two protomers, each binding to an IgE molecule. Importantly, this process elicits transcriptional activation of Egr1/3 and Ccl2 in rat basophils, which can be attenuated by inhibiting the IgE receptor dimer-to-monomer transition. Collectively, our study unveils the mechanism of antigen-independent, IgE-mediated receptor activation.
2024-11-30 | GSE278387 | GEO
Project description:Mast cells produce a large amount of several chemokines after cross-linking of FceRI and participate in the pathogenesis of allergic diseases. The objective of this study was to comprehensively investigate FceRI-mediated chemokine induction in human mast cells and the effect of a corticosteroid (dexamethasone) and a calcineurin inhibitor (FK506). Human peripheral blood-derived mast cells were stimulated with anti-IgE antibody in the presence of dexamethasone or FK506. Expression of eight chemokines was significantly induced in mast cells by anti-IgE stimulation. Induction of CCL2, CCL7, CXCL3 and CXCL8 by anti-IgE was significantly inhibited by dexamethasone. In contrast, induction of CCL1, CCL3, CCL4 and CCL18 was significantly inhibited by FK506. Combination of dexamethasone and FK506 suppressed production of all chemokines by anti-IgE stimulation. These results suggest that corticosteroids and calcineurin inhibitors inhibit expression of distinct subsets of chemokines and a combination of these drugs almost completely suppresses the induction of all chemokine genes in human mast cells in response to FceRI-dependent stimulation.
2009-03-12 | GSE15174 | GEO
Project description:Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy. dUTP mRNA-Seq profiles of indicated hematopoietic cell lineages were generated on Illumina HiSeq2500. Hematopoietic cells were isolated from Balb/C mice that developed food allergy and bone marrow-derived mast cells were generated from naïve Balb/C mice
2015-09-11 | E-GEOD-72921 | biostudies-arrayexpress
Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
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