The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity
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ABSTRACT:
PROVIDER: PRJNA971095 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24490400_1.fastq.gz | Fastqsanger.gz | |||
| SRR24490400_2.fastq.gz | Fastqsanger.gz | |||
| SRR24490395_1.fastq.gz | Fastqsanger.gz | |||
| SRR24490395_2.fastq.gz | Fastqsanger.gz | |||
| SRR24490396_1.fastq.gz | Fastqsanger.gz |
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Project description:The innate immune system functions as the first line of defense against cancer cells, particularly the detection and clearance of cancer cells by phagocytosis. The liver resident macrophages, known as Kupffer cells, have the largest population of body’s tissue resident macrophages and constitute the first line of defense against cancer cells invading the liver. However, the molecule mechanisms underlying the detection and phagocytosis of cancer cells by Kupffer cells are still unclear. Here, using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that Ermap expressed on cancer cells delivered the pro-phagocytosis ‘eat me’ signal to promote Kupffer cells phagocytosis and control over liver metastasis of various cancer cells. Ermap ligated Galectin-9 expressed on Kupffer cells surface in a glycosylation dependent manner. Galectin-9 further formed a bridging complex with Ermap and transmembrane receptor Dectin-2 expressed on Kupffer cells to promote the detection and phagocytosis of cancer cells by Kupffer cells. Patients with tumors expressing low ERMAP had more liver metastases. Thus, our study identifies the Ermap–Galectin-9–Dectin-2 axis as an ‘eat me’ signal for Kupffer cells to engulf cancer cells and control liver metastasis.
2023-08-03 | GSE232126 | GEO
Project description:Metastasis to distal organ is a fatal cause of cancer death and liver is one of the most common site of metastasis leading to bad prognosis. Although it has been known that innate immune cells play critical roles in the regulation of liver metastasis, how they control the tumor development is still largely unclear. We found that Dectin-2 (Clec4n), a C-type lectin receptor (CLR), suppresses liver metastasis and such Dectin-2-mediated anti-tumor rejection requires Kupffer cells, liver-residing macrophages, which express Dectin-2 dominantly in liver. We used microarray to examine comprehensive gene expressions induced by Dectin-2 when anti-tumoral Kupffer cells interact with cancer cells
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Project description:The multifunctional -galactoside-binding protein galectin-3 is found in many distinct subcellular compartments including the cell nucleus. Expression and distribution of galectin-3 between the cell nucleus and the cytosol changes during cell differentiation and cancer development. Nuclear functions of galectin-3 and how they contribute to tumorigenesis are not understood. In order to identify nuclear galectin-3 interaction partners, we used affinity chromatography and co-immunoprecipitation. Spatial proximity in the nucleus was assessed by immunofluorescence and proximity ligation assay. We also investigated the function of galectin-3 on mRNA-export by fluorescence in situ hybridization and on mRNA-processing by RNA-sequencing.
2016-06-07 | E-MTAB-4783 | biostudies-arrayexpress
Project description:Rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Dectin-1-mediated signaling stimulated characteristic gene expression, such as MCP-1, IL-4, IL-13, TNF-αand Nfkbiz. RBL-2H3 cell line stably expressing Dectin-1 was established. Non-stimulated cells (control) compared to Dectin-1-stimulated (Curdlan) cells in order to comfirm Dectin-1-mediated signaling-inducible genes. Dectin-1-stimulated cells compared to Syk inhibitor R406-pretreated cells in order to examine the importance of Syk for Dectin-1-mediated gene up-regulations.
2014-03-27 | E-GEOD-56246 | biostudies-arrayexpress
Project description:Infection by the Gram-negative bacterium Pseudomonas aeruginosa is common in hospitalized immunocompromised as well as immunocompetent ventilated patients and is often life-threatening because of resistance of the bacteria to antibiotics. This prompts the question whether the host’s immune system can be educated to combat this bacterium. Bacterial lipopolysaccharide (LPS) is known to promote host resistance to bacterial infections although an understanding of the underlying mechanism is lacking. Here we show that prior exposure to a single low dose of LPS protects mice from a lethal infection by P. aeruginosa. These mice displayed expansion of a neutrophil and an interstitial macrophage population that were barely detectable in mice that did not receive LPS prior to infection. Both cell populations were distinguishable from other immune cell populations by being enriched in gene sets that included phagocytosis- and cell-killing-associated genes. The cell killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging of neutrophils for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Interrogating the relevance of these findings in hospitalized patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs. Taken together, our study provides impetus to harnessing the potential of galectin-3-expressing neutrophils to protect the lung from lethal infections and respiratory failure.
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Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98814 | GEO
Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98825 | GEO
Project description:Innate immune pattern recognition receptors play critical roles in pathogen detection and initiation of antimicrobial responses. We and others have previously demonstrated the importance of the beta-glucan receptor Dectin-1 in the recognition of pathogenic fungi by macrophages and dendritic cells, and have elucidated some of the mechanisms by which Dectin-1 signals to coordinate the antifungal response. While Dectin-1 signals alone are sufficient to trigger phagocytosis and Src-Syk-mediated induction of antimicrobial reactive oxygen species, collaboration with Toll-like receptor (TLR)2 signaling enhances NF-kB activation and regulates cytokine production. In this study we demonstrate that Dectin-1 signaling can also directly modulate gene expression via activation of nuclear transcription of activated T cells (NFAT) transcription factors. Dectin-1 ligation by zymosan particles or live Candida albicans yeast triggers NFAT activation in macrophages and dendritic cells. Dectin-1-triggered NFAT activation plays a role in the induction of Egr2 and Egr3 transcription factors, and cyclooxygenase 2 (Cox-2). Furthermore, we show that NFAT activation regulates IL-2, IL-10 and IL-12 p70 production by zymosan-stimulated dendritic cells. These data establish NFAT activation in myeloid cells as a novel mechanism of regulation of the innate antimicrobial response. Experiment Overall Design: Bone marrow-derived macrophages deficient in MyD88 were stimulated with zymosan, and total RNA was extracted 120 minutes after stimulation for comparison to macrophages grown under the same conditions, but not stimulated.
2008-06-14 | E-GEOD-6376 | biostudies-arrayexpress
Project description:Purpose: To characterize Card9-dependent and Card9-independent Dectin-1 mediated gene expression changes in neutrophils and to compare response to Dectin-1 stimulation in neutrophils and macrophages. Method: BM neutrophils from WT and Card9-/- mice were isolated by MACS column purification and treated with or without the Dectin-1 agonist, curdlan for 3 hrs. WT BM-derived macrophages were also treated with or without curdlan for 3hrs before sample collection. Results: We identified both Card9-dependent and Card9-independent gene expression changes with Dectin-1 stimulation in neutrophils. We also identified cell-type specific differences in the response to Dectin-1 stimulation in neutrophils and macrophages. Conclusions: Dectin-1 stimulation induces significant gene expression changes regulated by either canonical Card9-dependent or non-canonical Card9-independent mechanisms.
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Project description:Rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Dectin-1-mediated signaling stimulated characteristic gene expression, such as MCP-1, IL-4, IL-13, TNF-αand Nfkbiz.
2014-03-27 | GSE56246 | GEO