Analysis of gene expressions of mast cells in murine atopic dermatitis-like skin
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE180541 | GEO | 2022/09/09
REPOSITORIES: GEO
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Project description:Cutaneous mast cells (MC) mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We found that Langerhans cell (LC)-deficient mice have reduced numbers of MrgprD-expressing epidermal nerve endings and manifest enhanced irritant dermatitis due to exaggerated MC degranulation. Ablation of LC or MrgprD-expressing neurons increased expression of a MC gene module including the activating receptor, Mrgprb2, resulting in increased MC degranulation and cutaneous inflammation in multiple models. β-alanine agonism of MrgprD-expressing neurons reduced expression of MC module genes and suppressed MC responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism and decreased in LC-deficient mice. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive MC and a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress MC hyperresponsiveness and skin inflammation via glutamate release thereby revealing an unexpected neuro-immune mechanism maintaining cutaneous immune homeostasis.
2021-03-23 | GSE165295 | GEO
Project description:Although mast cells elicit proinflammatory and type I IFN responses upon VSV infection, in response to L.monocytogenes (L.m) or S. Typhimurium (S.t), such cells elicit a transcriptional program devoid of type I IFN response. Balanced induction of proinflamatory and type I interferon (IFN) responses upon activation of Toll like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmune syndromes. However, their potential role in anti-microbial host defenses is increasingly being acknowledged. How mast cells interact with microbes and the nature of responses triggered thereof is not well characterized. Here we show that in response to TLR activation by Gram-positive and negative bacteria or their components like LPS, unlike macrophages, mast cells elicit pro-inflammatory but not type I IFN responses. We demonstrate that in mast cells, the bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization - a prerequisite for type I IFN induction. Such cells could, however, elicit type I IFNs in response to vesicular stomatitis virus (VSV), which accesses the cytosolic RIG-I receptor. Although important for anti-viral immunity, a strong type I IFN response is known to contribute to pathogenesis during bacterial infection. Thus, while endowed with the capacity to elicit type I IFNs in response to viral infection, the fact that mast cells only elicit pro-inflammatory responses upon bacterial infection illustrates that mast cells, key effector cells of the innate immune system, are well adjusted for optimal anti-bacterial and anti-viral responses. Wild type control (cntr) or interferon receptor (IFNAR)-deficient mast cells (MC) or macrophages (MAC) were infected with L.m. and S.t. (MOIs 50 and 5 for MC and MAC, respectively). MC and MAC were exposed to VSV-AV2 (MOI: 2). Samples were analyzed after 6 hours. Uninfected/unstimulated cells were used as reference samples for calculating fold change in gene expression. Gene Expression levels were determined by the Affymetrix MOE 430 2.0 GeneChips. Signal Intensities were calculated using the RMA algorithm and for statistical analysis we applied GeneSpring GX 10 software suite (Agilent Technologies, Waldbronn, Germany). MultiExperiment Viewer (MEV) software version 4.4 of the Institute for Genomic Research was used for clustering algorithm data analysis and visualization.
2009-12-31 | E-GEOD-18500 | biostudies-arrayexpress
Project description:Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of humans.
2015-12-21 | GSE71247 | GEO
Project description:Atopic dermatitis is a common chronic inflammatory skin disease characterized by infiltration of inflammatory cells, extensive pruritus and a clinical course of symptomatic flares and remissions. Berberine (BER), a naturally occurring isoquinoline alkaloid, has many pharmacological effects including inhibition of protein synthesis, cell cycle arrest, and anti-inflammatory activities. However, a detailed molecular mechanism underling the anti-inflammatory action of BER in inflammatory cells is unclear. Here, to identify genes involved in the anti-inflammatory effects of BER in DNP-activated mouse MC/9 mast cells, global-scale gene expression analysis was carried out using a GeneChipî system. Mouse MC/9 mast cells were treated with BER (10 microM), DNP (anti-DNP IgE, Sigma; 500 microg/ml) or a combination of BER and DNP. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was analyzed by an Affymetrix GeneChipî system with a Mouse Genome 430 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturerâÂÂs instructions.
2015-12-22 | E-GEOD-76202 | biostudies-arrayexpress
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:Hematopoiesis occurs in distinct waves. ‘Definitive’ hematopoietic stem cells (HSC) with the potential for all blood lineages emerge in the aorta-gonado-mesonephros (AGM), while ‘primitive’ progenitors, whose potential is thought to be limited to erythrocytes, megakaryocytes and macrophages (MΦ), arise earlier in the yolk sac (YS). Here, we questioned whether other YS lineages exist that have not been identified, partially owing to limitations of current lineage tracing models. We established the use of Cdh5CreERT2 for hematopoietic fate mapping, which revealed the YS origin of mast cells (MC). YS derived MC are replaced by definitive MC, which maintain themselves independently from the BM in the adult. Replacement occurs with tissue specific kinetics. MC in the skin, but not other organs, remain largely YS derived prenatally and are phenotypically and transcriptomically distinct from definite adult MC. We conclude that dual hematopoietic origin is not MΦ specific, but shared between these two myeloid lineages.
2018-06-01 | GSE104790 | GEO
Project description:Purpose: The goals of this study are to investigate the effect of PKM2 KO or TMEM33 overexpression on genes expression. Methods: Fresh PKM2 KO MCF7, PKM2 KO MDA-MB-231 and TMEM33 OE MDA-MB-231 cell pellets, and their respective parental cells, were used for RNA extraction. RNA sequencing libraries were prepared using the Illumina TruSeq RNA Library Prep Kit v2 following the manufacturer’s instructions. Each library was sequenced in single read mode, 1 x 50 bp, using the HiSeq4000 platform. Sequencing reads were aligned to human genome (hg38) by STAR (version 2.5.2b). Expression levels of genes annotated in GENCODE (version 24 for PKM2 KO and their parental cells; version 27 for TMEM33 OE and their control cells) were quantified by RSEM (version 1.3.0). Parameters of STAR and RSEM were set following ENCODE’s long RNA-seq processing pipeline. Differentially expressed genes were identified by DESeq2 (version 1.24.0) under the requirement of at least two-fold changes and an adjusted p-value < 0.05. Results: Differential gene expression analyses identified 269 and 504 significantly up-regulated and 204 and 289 significantly down-regulated genes in MDA-MB-231 and MCF7 PKM2 KO cells compared to their parental cells (>=2-fold, adjusted P value < 0.05); Gene set enrichment analysis (GSEA) showed that cholesterol homeostasis and fatty acid metabolism were among the top down-regulated pathways in MDA-MB-231 TMEM33 OE cells. Moreover, the differential gene expression profiles between PKM2 KO and TMEM33 OE cell lines were positively correlated. Notably, the mRNAs of genes related to cholesterol homeostasis were decreased in both PKM2 KO and TMEM33 OE cells. Conclusions: TMEM33 acts as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism.
2021-08-06 | GSE175956 | GEO
Project description:Exosomes are vesicles of endocytic origin released by many types of cells into the extracellular environment. In an attempt to further examine the exosome-mediated cellular communication, we show that exosomes from a mouse mast cell line (MC/9), exosomes from primary bone marrow derived mast cells, and exosomes from a human mast cell line (HMC-1) contain RNA but not DNA. Microarray assessments of exosome-derived RNA revealed that these vesicles contain mRNA from approximately 1200 genes, many of which are unique and not present in the cytoplasmic RNA pool in the donor cell. Experiment Overall Design: Exosomes were prepared from the supernatant of MC/9 cells by differential centrifugations and filtration. RNA was isolated from the exosomes and their parental cells using Trizo. The microarray experiments were performed by SweGene (www.swegene.org/) according to Affymetrix microarray DNA chip analysis. The experiment was performed in quadruple samples. ExoRNA1, ExoRNA2, ExoRNA3, and ExoRNA4 for the exosomes samples and Mast_cells1, Mast_cells2, Mast_cells3, and Mast_cells4 for the MC/9 cells.
2008-06-15 | E-GEOD-7275 | biostudies-arrayexpress
Project description:Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.
2017-09-15 | GSE89395 | GEO