Gene expression data of human peripheral blood-derived cultured mast cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE71247 | GEO | 2015/12/21
SECONDARY ACCESSION(S): PRJNA290845
REPOSITORIES: GEO
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Project description:Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec‐8‐mediated inhibition in primary MCs using an anti‐Siglec‐8 monoclonal antibody (mAb). Phospho‐proteomic profiling of FcεRI‐activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec‐8 was found to directly interact with FcεRI signaling molecules. Siglec‐8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI‐induced phosphorylation events through phosphatase recruitment and interaction with FcεRI, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
2022-01-21 | PXD030820 | Pride
Project description:Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease. Mouse bone marrow-derived mast cells treated with IL3 or IL3+IL33. 6 replicates each.
2013-02-06 | E-GEOD-39382 | biostudies-arrayexpress
Project description:In contrast to their clearly defined roles in allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remain enigmatic. Recent research supports the toxin hypothesis, showing that MCs and IgE-related type 2 immune responses can enhance host defense against certain noxious substances, including honeybee venom (BV). However, the mechanisms by which MCs can interfere with BV toxicity are unknown. In this study, we assessed the role of IgE and certain MC products in MC-mediated BV detoxification. We applied in vitro and in vivo fluorescence microscopy imaging, and flow cytometry, fibroblast-based toxicity assays and mass spectrometry to investigate IgE-mediated detoxification of BV cytotoxicity by mouse and human MCs in vitro. Pharmacologic strategies to interfere with MC-derived heparin and proteases helped to define the importance of specific detoxification mechanisms. Venom-specific IgE increased the degranulation and cytokine responses of MCs to BV in vitro. Passive serum sensitization enhanced MC degranulation in vivo. IgE-activated mouse or human MCs exhibited enhanced potential for detoxifying BV by both proteolytic degradation and heparin-related interference with toxicity. Mediators released by IgE-activated human MCs efficiently degraded multiple BV toxins. Our results both reveal that IgE sensitization enhances the MC’s ability to detoxify BV and also assign efficient toxin-neutralizing activity to MC-derived heparin and proteases. Our study thus highlights the potential importance of IgE, MCs, and particular MC products in defense against BV.
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Project description:Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
2013-02-06 | GSE39382 | GEO
Project description:We developed a novel strategy for the rapid and efficient differentiation of MCs from human induced pluripotent stem cells (hiPSC). These hiPSC-derived MCs (hiPSC-MCs) exhibit phenotypic and functional characteristics of human skin MCs (hsMCs) and peripheral hematopoietic stem cell-derived MCs (PSCMCs). hiPSC-MCs display stable expression of MC-associated receptors such as CD117, FcεRIα and MRGPRX2, and degranulate by stimulation with IgE/anti-IgE and Substance. P.
2022-08-31 | GSE181457 | GEO
Project description:Uterine Mast cells (MCs) are essential for placentation, implantation and growth of fetus. In contrast, the functions of placental MCs are poorly investigated. The objective of the study was to evaluate the transcriptional profile of human placental MCs using whole genome microarray. We isolated MCs from placenta from healthy at term donors with CD117 and IgE antibodies, and used HMC-1.2 cell lines as controls. Data analysis revealed 16,468 genes modulated in human placenta MCs as compared with HMC-1.2 cell lines; most of them (83%) were up-regulated. The differentially expressed genes in placental MCs were enriched with three biological categories: immune response, FcReI signaling and reproduction processes. The two first categories revealed the importance of immune gene expression including chemokines, cytokines, interferon, and major histocompatibility complex antigens in placental MCs. A set of genes were modulated in FcReI process suggesting a role of IgE-mediated activation. Finally, in pregnancy category, we identified specific genes of WNT pathway and those involved in response to estrogen and progesterone. Taken together, human placental MCs exhibited a unique transcriptional profile enriched with immune response and pregnancy genes, which reflects the impact of placenta environment on MC functions.
2019-12-31 | GSE111346 | GEO
Project description:Degranulating mast cells (MCs) release inflammatory mediators (proteins, lipids, small molecules), including chemokines and chemoattractants, which recruit other immune cells in tissues. Neutrophils can initiate self-amplifying swarming responses via intercellular communication through the lipid leukotriene B4 (LTB4). Initially discovered by two-photon intravital microscopy in mice and confocal live cell imaging, we show that degranulating MCs release LTB4 and exploit this attractant by re-directing neutrophils to MCs. In a process generally termed entosis, neutrophil cluster formation around MCs results in the trapping of living neutrophils inside MC vacuoles in vivo and in vitro. Thus, we identify a novel cell-in-cell structure between MCs and neutrophils, which we term “Mast Cell Intracellular Trap” (MIT). Compared to MCs, MITs revealed improved MC metabolism and recovery after degranulation. This leads to several benefits for MITs: (1) they can be more efficiently re-stimulated than MCs, (2) they show improved survival under nutrient limitation, and (3) MITs store neutrophil proteins, DNA and effector molecules, which can be released after re-stimulation. In this context, we compare the secretome (secreted proteins) of MCs and MITs (in cell culture) before and subsequent to degranulation via label-free nanoLC-MS. In summary, mast cells trap and cannibalize swarming neutrophils, which supply nutrients, proteins and inflammatory molecules to recovering MCs. Our studies may have potential implications for chronically activated MCs in MC-related immune disorders.
2024-06-18 | PXD044140 | Pride
Project description:Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs) which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remains poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs, isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed overexpression of SAMD14 in HMC-1 MCs altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data presents the first profile of human MCs derived from patient prostate cancer specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.
2021-03-12 | PXD022782 | Pride
Project description:Effector CD4+ T lymphocytes (Teff) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells strategically located near blood vessels and T cell rich areas. MC/Teff cells interactions shape Teff cell responses but in turn, Teff cell action on MC is still poorly understood. Here, we analyzed the human MC/Teff cells interplay through the application of RNAseq and functional assays and showed that activated Teff cells induced a specific transcriptomic program in MCs driving them toward an inflammatory phenotype. Teff cells affected key MC immune functions as they induced prostaglandin, inflammatory cytokines and chemokines production and fostered FceRI-dependent degranulation. Moreover, Teff cell induced in MCs the capacity to regulate T cell responses through a wide-range of dedicated soluble and membrane ligands. Cell-Cell communication inference based on transcriptomic data indicated that IFN-g, IL-21, IL-27 and IL-1b were the main driver of MC differentiation program.
2024-07-03 | GSE235240 | GEO
Project description:Rationale: Mast cells (MCs) within the airway epithelium in asthma are closely related to airway dysfunction, but crosstalk between airway epithelial cells (AECs) and MCs in asthma remains incompletely understood. Human rhinovirus (HRV) infections are key triggers for asthma progression and AECs from individuals with asthma may have dysregulated anti-viral responses. Objectives: We utilize primary phenotyped AECs in an ex vivo coculture model system to examine crosstalk between AECs and MCs following epithelial HRV infection. Methods: Primary AECs were obtained from children with asthma (n=11) and healthy children (n=10), differentiated at air-liquid interface, and cultured in the presence of laboratory of allergic diseases-2 (LAD2) MCs. AECs were infected with HRV serogroup A 16 (HRV16) for 48 hours. RNA isolated from both AECs and MCs underwent RNA-sequencing (RNAseq) analysis. Direct effects of epithelial-derived interferons on LAD2 MCs were examined by qPCR. Results: MCs increased expression of pro-inflammatory and anti-viral genes in AECs. AECs demonstrated a robust antiviral response following HRV16 infection that resulted in significant changes in MC gene expression, including upregulation of genes involved in anti-viral responses, leukocyte activation, and type-2 (T2) inflammation. Subsequent ex vivo modeling demonstrated that IFN-β induces MC IL13 expression. The effects of AEC phenotype were small relative to the effects of viral infection and the presence of MCs. Conclusions: There is significant crosstalk between AECs and MCs, which are present in the epithelium in asthma. Epithelial-derived interferons not only play a role in viral suppression, but further alter MC immune responses including specific T2 genes.
2022-06-22 | GSE206680 | GEO