Circadian transcriptional profile of tissues with and without neutrophil depletion
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198770 | GEO | 2025/01/09
REPOSITORIES: GEO
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Project description:Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: approximately 15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.
2007-10-02 | E-GEOD-2322 | biostudies-arrayexpress
Project description:Neutrophils are increasingly recognized as key players in the tumour immune response, and are associated with poor clinical outcomes. Multiple studies have characterised various neutrophil states within the tumor, with associated pro- and anti- tumoral functions. However, it is unknown if this heterogeneity of neutrophils is contributed by their surrounding tumor microenivironment. To answer this, we performed 10X Visium spatial transcriptomics on a murine model of pancreatic cancer. We discovered that terminally differentiated T3 neutrophils localise primarily in regions near hypoxic and glycolytic areas, while transitional immature T1 and mature T2 neutrophils localise towards the peripheral regions of the tumors. This results points to a spatially dependent role of T3 neutrophils, which may be critical to carry out pro-tumorigenic functions.
2024-01-11 | GSE244534 | GEO
Project description:Our study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)).
2018-09-28 | GSE106349 | GEO
Project description:Mass Spectrometry identifies temporal changes and hallmarks of Delayed Recovery in the COVID19 Neutrophil proteomes MTD project_description High-resolution mass spectrometry and the parallel quantitative evaluation of thousands of proteins has been used to characterise the proteomes of peripheral blood neutrophils from >200 individuals. This work has comprehensively mapped neutrophil molecular changes associated with mild versus severe COVID19 and identified significant quantitative changes in more than 1700 proteins in neutrophils from patients hospitalised with COVID19 versus patients with non-COVID19 acute respiratory infections. The study identifies neutrophil protein signatures associated with COVID19 disease severity. The data also show that alterations in neutrophil proteomes can persist in fully recovered patients and identify distinct neutrophil proteomes in recovered versus non recovered patients. Our study provides novel insights into neutrophil responses during acute COVID-19 and reveal that altered neutrophil phenotypes persist in convalescent COVID19 infections.
2022-08-17 | PXD036089 | Pride
Project description:During systemic inflammation, different neutrophil subsets are mobilized to the blood circulation. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16bright/CD62Lbright) based on either an immature CD16dim/CD62Lbright or a CD16bright/CD62Ldim phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex vivo, but the underlying mechanism is largely unknown. We performed transcriptome analysis on the different neutrophil subsets to identify changes that are relevant for their functions. Neutrophil subsets were isolated by FACS sorting from the blood of healthy volunteers who were administered a single dose of lipopolysaccharide (LPS). The transcriptome was determined by microarray. The mobilized neutrophil subsets were characterized by specific transcriptome profiles reflecting their phase in neutrophil lifespan. Interestingly, the CD16bright/CD62Ldim suppressive neutrophils showed an interferon-induced transcriptome profile. This was confirmed by stimulation of peripheral neutrophils with IFNgamma. These cells acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that the suppressive phenotype of the neutrophil subset is induced by IFNgamma. Specific stimulation of neutrophils might have a pivotal role in regulating lymphocyte-mediated inflammation and autoimmune disease. After LPS infusion, blood was taken at t=0 and t=4 hours. Neutrophils were FACS sorted based on CD16 and CD62L expression. Gene expression of neutrophil subsets was assessed relative to t=0 as control.
2013-05-01 | E-GEOD-42358 | biostudies-arrayexpress
Project description:To investigate the effect of the absence of neutrophils in the transcriptome of fibroblast and macrophage from lung and skin we injected DT to Mrp8 CRE+ iDTR and Mrp8 CRE- iDTR mice every two days for a week and isolated lung and skin fibroblasts and macrophages by cell sorting . We then performed gene expression profiling analysis using data obtained from RNA-seq of macrophages and fibroblast 7 days after DT treatment and compared the transcriptomes of macrophages and fibroblasts in control or neutrophil depletion animals. We focused on the role of neutrophils on the regulation of extracelular matrix genes in fibroblasts and macrophages and found that neutrophil depletion does not significantly affect the RNA level of matrix-related transcripts in those cells.
2025-01-09 | GSE202738 | GEO
Project description:Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function is directly affected by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors has been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n=6) and people with RA (n=7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h. Metabolites were extracted and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models show a divergent metabolic pattern in RA neutrophils compared to HC at baseline (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p-value<0.05). Bacterial killing was not inhibited by JAK inhibitors, indicating their effect on neutrophils is beneficial to inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.
2023-07-11 | MTBLS4766 | MetaboLights
Project description:Neutrophils, key cells of the innate immune system, are responsible for preventing bacterial infections. It has recently been established that neutrophils are capable of complex changes in gene expression during inflammation. The concept that neutrophils merely respond to external signals has been replaced by the concept that activated neutrophils can secrete a variety of cytokines and also have an active regulatory role in angiogenesis and tumoural fate. Currently, neutrophil research relies mostly in animal models that reproduce human physiology and pathology. Although, in many respects, there is a conservation of functions in mice and humans, little is known about genomic conservation of neutrophils between mice and humans. We hypothesize that neutrophils are transcriptionally active cells that alters their gene expression profile as they migrate into different compartments. To identify changes in neutrophil gene expression in the circulation and inflamed tissue we used recent advances in neutrophil isolation, RNA amplification and microarray technologies that allowed us to compare the transcriptome of neutrophils. Additionally, using bioinformatics, we investigate the genomic conservation of neutrophils between mice and humans. Total RNA obtained from isolated neutrophils from Bone Marrow, Blood and Peritoneal Exudate from Black 6 mice.
2013-03-30 | E-GEOD-43513 | biostudies-arrayexpress
Project description:Purpose: Identification of neutrophils at different stages of maturation and their phenotypic and functional differences remain unknown. The goal of this study was to confirm maturation status of Ly6GIntermediate, Ly6GHigh and Ly6G+ neutrophils, the consistency of this means of identication in disease, and identify functional differences. Methods: Ly6G+, Ly6GIntermediate and Ly6GHigh neutrophil populations were isolated by FACS into individual cell populations from PBS controls, acute-LPS inflammation and pancreatic adenocarcinoma (PDAC) bearing mouse tissues (metastatic KPC, non-metastatic KPflC and WT controls). RNA-Sequencing was performed on bulk isolated populations Results: We identified Ly6GIntermediate as bona-fide immature neutrophils and analysis of Ly6G expression level as a consistently accurate marker of identifying neutrophil maturity. Gene expression was influenced by maturation stage, tissue of isolation, developmental niche and pathology. Function associated expression differences were maintained between Ly6GIntermediate and Ly6GHigh neutrophils throughout tissues and pathology.
2021-07-28 | GSE180824 | GEO
Project description:Lipocalin 24p3 (24p3) is a neutrophil secondary granule protein. 24p3 is also a siderocalin, which binds several bacterial siderophores. It was therefore proposed that synthesis and secretion of 24p3 by stimulated macrophages or release of 24p3 upon neutrophil degranulation sequesters iron-laden siderophores to attenuate bacterial growth. Accordingly, 24p3-deficient mice are susceptible to bacterial pathogens whose siderophores would normally be chelated by 24p3. Specific granule deficiency (SGD) is a rare congenital disorder characterized by complete absence of proteins in secondary granules. Neutrophils from SGD patients, who are prone to bacterial infections, lack normal functions but the potential role of 24p3 in neutrophil dysfunction in SGD is not known. Here we show that neutrophils from 24p3-deficient mice are defective in many neutrophil functions. Specifically, neutrophils in 24p3-deficient mice do not extravasate to sites of infection and are defective for chemotaxis. A transcriptome analysis revealed that genes that control cytoskeletal reorganization are selectively suppressed in 24p3-deficient neutrophils. Additionally, small regulatory RNAs (miRNAs) that control upstream regulators of cytoskeletal proteins are also increased in 24p3-deficient neutrophils. Further, 24p3-deficient neutrophils failed to phagocytose bacteria, which may account for the enhanced sensitivity of 24p3-deficient mice to both intracellular (Listeria monocytogenes) and extracellular (Candida albicans, Staphylococcus aureus) pathogens. Interestingly, Listeria does not secrete siderophores and additionally, the siderophore secreted by Candida is not sequestered by 24p3. Therefore, the heightened sensitivity of 24p3-deficient mice to these pathogens is not due to sequestration of siderophores limiting iron availability, but is a consequence of impaired neutrophil function. Key words: Lipocalin, 24p3, neutrophils, cell motility, chemotaxis, MIRNA-362-3p To address the role of lipocalin 2 in regulating miRNA expression profiling in neutrophils derived from mouse bone marrow, we performed microarray analysis of miRNAs in wild type (N=2) and lcn2 knockout (N=2) neutrophils.
2013-01-31 | E-GEOD-43890 | biostudies-arrayexpress