Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA386315 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity
| PRJNA386319 | ENA
Project description:Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity [mouse]
| PRJNA386316 | ENA
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: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:TC-510 is a novel cell therapy that consists of autologous genetically engineered T cells expressing two synthetic constructs: first, a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex and second, a PD-1:CD28 switch receptor, which is expressed on the surface of the T cell, independently from the TCR. The PD-1:CD28 switch receptor comprises the PD-1 extracellular domain fused to the CD28 intracellular domain via a transmembrane domain. Thus, the switch is designed to produce a costimulatory signal upon engagement with PD-L1 on cancer cells.
| 2740481 | ecrin-mdr-crc
Project description:<p>Molecularly-targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signaling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumors. AR-GSRs occur in the context of copy-neutral and amplified AR and display heterogeneity in breakpoint location, rearrangement class, and sub-clonal enrichment in tumors within and between patients. Despite this heterogeneity, one common outcome in tumors with high sub-clonal enrichment of AR-GSRs is outlier expression of diverse AR variant species lacking the ligand binding domain and possessing ligand-independent transcriptional activity. Collectively, these findings reveal AR-GSRs as important drivers of persistent AR signaling in CRPC.</p>
| phs001223 | dbGaP
Project description:Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. b-glucan, a Dectin-1 ligand purified from the Candida albicans cell wall, has been one of the most widely utilized and well-characterized ligands for inducing innate immune memory. However, many Dectin-1 agonists exist, and it is not known whether all Dectin-1 ligands produce the same phenotype. Using a well-established in vitro model of trained immunity, we compared two commercially available Dectin-1 agonists with the gold standard b-glucan represented in the literature. We found that depleted zymosan, a b-glucan purified from the Saccharomyces cerevisiae cell wall through alkali treatment, produced near identical training effects as C. albicans b-glucan. However, untreated zymosan produced a distinct training effect from b-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of key cytokines such as TNF, IL-12, and IL-6. Zymosan activated NFkB and AP-1 transcription factors more strongly than b-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of b-glucans to a phenotype resembling training with zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1. These findings bring clarity to the specific question of which Dectin-1 agonists produce prototypical training effects and provides broader insight into how signaling networks regulate innate immune training at large.
2024-01-29 | GSE242947 | GEO
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFκB by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by TL1A.
2018-08-24 | GSE118958 | GEO
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFκB by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated with inflammatory cytokines such as TNFα or IL-1β inhibits Fas-induced apoptosis. In contrast, DcR3 inhibited cell proliferation induced by inflammatory cytokines via membrane-bound TL1A expressed on RA-FLS. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of TL1A.
2014-12-10 | GSE63995 | 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