Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA383371 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5454410.fastq.gz | Fastqsanger.gz | |||
| SRR5454411.fastq.gz | Fastqsanger.gz | |||
| SRR5454412.fastq.gz | Fastqsanger.gz | |||
| SRR5454413.fastq.gz | Fastqsanger.gz | |||
| SRR5454414.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
Project description:Western diet triggers NLRP3-dependent persistent functional reprogramming of myeloid cells
| PRJNA383354 | ENA
Project description:Western diet triggers NLRP3-dependent persistent functional reprogramming of myeloid cells [RNA-Seq]
| PRJNA383373 | ENA
Project description:Western diet triggers NLRP3-dependent persistent functional reprogramming of myeloid cells II [RNA-Seq]
| PRJNA418042 | ENA
Project description:Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases.
2018-01-17 | GSE97925 | GEO
Project description:Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases.
2018-01-17 | GSE97924 | GEO
Project description:Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases.
2018-01-17 | GSE106789 | GEO
Project description:Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, present auto-inflammation and its manifestation is largely dependent on environmental cues. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowers the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increases NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protects mice from gouty arthritis. Activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux promoting NLRP3 inflammasome activation. Activation of PIEZO signaling is sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Finally, pharmacologic inhibition of KCNN4 alleviates auto-inflammation in CAPS patient cells and in CAPS-mimicking mice. Thus, PIEZO-dependent mechanical inputs augment inflammation in NLRP3-dependent diseases including CAPS.
2023-10-26 | GSE246208 | GEO
Project description:Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to the increasing prevalence of these diseases yet the mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. ATAC-seq profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings demonstrate that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan.
2023-03-13 | GSE219095 | GEO
Project description:<p><strong>BACKGROUND:</strong> Cryopyrin-Associated Periodic Syndrome (CAPS) is an autoinflammatory condition consequence of monoallelic variants in the NLRP3 gene that exacerbate IL-1β production. These variants are gain-of-function, but the exact regulatory mechanism of the NLRP3 CAPS-inflammasome is not well yet understood. It is considered as a hypersensitive inflammasome triggered by cell priming, but patients with CAPS and animal disease models present inflammatory flares in the absence of external triggers.</p><p><strong>OBJECTIVES:</strong> To study the regulation and activation of the NLRP3 inflammasome in CAPS.</p><p><strong>METHODS:</strong> CAPS derived blood samples and genetically modified macrophages expressing different NLRP3 CAPS-associated variants were used to assess NLRP3 function dissociated from cell priming and cell metabolism.</p><p><strong>RESULTS:</strong> We found that CAPS-associated variants constitutively result in active NLRP3 inflammasomes, that induce a basal cleavage of gasdermin D, IL-18 release and pyroptosis. The constitutive active NLRP3 inflammasome was blocked by MCC950 and was dependent on NLRP3 expression level, being further regulated by deubiquitination. We also showed that activation of NF-κB with lipopolysaccharide or other endogenous host-derived molecules (palmitate, S100A9 or IL-6) further modulated the activation of the NLRP3 CAPS inflammasome and expanded the repertoire of molecules secreted from CAPS macrophages to IL-1β, IL-1α, HMGB1, cystatin B and the P2X7 receptor, identifying novel proteins involved in CAPS pathogenesis. NLRP3 inflammasomes with CAPS associated variants affected the immunometabolism of the myeloid compartment and impaired glycolysis.</p><p><strong>CONCLUSIONS:</strong> These findings demonstrate that NLRP3 CAPS-associated variants form a constitutive active inflammasome that induce basal pyroptosis and IL-18 release without cell priming, suggesting a priming-independent mechanism for the initiation of CAPS flares characterized with a profound affection in the immunometabolism.</p>
2024-01-09 | MTBLS7872 | MetaboLights
Project description:S100A8/A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is still elusive. We report here that E-selectin-induced rapid S100A8/A9 release during inflammation occurs in a NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton?s tyrosine kinase dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel KV1.3 mediates ASC oligomerization. This is followed by caspase-1 cleavage and downstream activation of pore forming gasdermin D, enabling cytosolic S100A8/A9 to be released. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death, but is a transient process involving activation of the ESCRT-III membrane repair machinery. These findings do not only elucidate the molecular mechanisms of controlled S100A8/A9 release but also identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation.
2023-10-25 | PXD041652 | Pride