Neutrophil plasticity
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB21513 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2102760.fastq.gz | Fastqsanger.gz | |||
| ERR2102751.fastq.gz | Fastqsanger.gz | |||
| ERR2102761.fastq.gz | Fastqsanger.gz | |||
| ERR2102752.fastq.gz | Fastqsanger.gz | |||
| ERR2102762.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 19 |
Similar Datasets
Project description:Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2α-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2α-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.
2020-06-04 | GSE151703 | GEO
Project description:Toll-like receptor (TLR) agonists have received considerable attention as therapeutic targets for cancer immunotherapy owing to their ability to convert immunosuppressive tumor microenvironments towards a more T-cell inflamed phenotype. However, TLRs differ in their cell expression profiles and intracellular signaling pathways, raising the possibility that distinct TLRs differentially influence the tumor immune microenvironment.
2021-07-16 | GSE179449 | GEO
Project description:In this study, we used chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3-marked, to identify various TSSs associated with LPS-, TNF-alfa- and IL-10-stimulated neutrophils from healthy individuals, as well as neutrophils derived from the patients with sepsis (systemic septic inflammation with LPS-stimulated neutrophils), NMOSD (aseptic inflammation with neutrophils pre-activated by TNF-alfa and periodontitis (localized self-limiting septic inflammation with IL-10-positive neutrophils). We provided comprehensive epigenomic analysis within H3K4me3- marked histone that allowed us to identify human neutrophil regulators affecting their plasticity during inflammation as well as suppression.
2021-10-27 | GSE186508 | GEO
Project description:Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancers exhibited much more spontaneous migration to tissues. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and much more production of ATP. Their enhanced spontaneous migration was mediated by the binding of ATP to purinergic receptors. In ectopic tumor models and the late stages of cancers, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed in neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils’ contribution to early tumor dissemination.
2018-09-27 | GSE118366 | GEO
Project description:Chronic inflammatory milieu in the tumor microenvironment (TME) leads to the recruitment and differentiation of myeloid-derived suppressor cells (MDSCs). Polymorphonuclear (PMN)-MDSCs, which are phenotypically and morphologically defined as a subset of neutrophils, cause major immune suppression in the TME, posing a significant challenge in the development of effective immunotherapies. Despite recent advances in our understanding of PMN-MDSC functions, the mechanism that gives rise to immunosuppressive neutrophils within the TME remains elusive. Both in vivo and in vitro, newly recruited neutrophils into the tumor sites remained activated and highly motile for several days and developed immunosuppressive phenotypes, as indicated by increased arginase 1 (Arg1) and dcTrail-R1 expression and suppressed anti-cancer CD8 T cell cytotoxicity. The strong suppressive function was successfully recapitulated by incubating naïve neutrophils with cancer cell culture supernatant in vitro. Cancer metabolite secretome analyses of the culture supernatant revealed that both murine and human cancers released lipid mediators to induce the differentiation of immunosuppressive neutrophils. Liquid chromatography–mass spectrometry (LC-MS) lipidomic analysis identified platelet activation factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) as a common tumor-derived lipid mediator that induces neutrophil differentiation. Lysophosphatidylcholine acyltransferase 2 (LPCAT2), the PAF biosynthetic enzyme, is upregulated in human pancreatic ductal adenocarcinoma (PDAC) and shows an unfavorable correlation with patient survival across multiple cancer types. Our study identifies PAF as a novel lipid-driven mechanism of MDSC differentiation in the TME, providing a potential target for cancer immunotherapy.
2024-09-13 | GSE273979 | GEO
Project description:APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD) with increased odds ratios in females. Targeting amyloid plaques show modest improvement in male non-APOE4 carriers. Leveraging single cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female AD patients, we identify a new subset of neutrophils, interacting with microglia associated with cognitive impairment. This phenotype is defined by increased IL-17 and IL-1 co-expressed gene modules in blood neutrophils and in microglia of cognitively impaired female APOE e4 carriers, showing increased infiltration to the AD brain. APOE4 female IL-17+ neutrophils upregulated the immunosuppressive cytokines IL-10 and TGFb, and immune checkpoints including LAG-3 and PD-1, associated with accelerated immune aging. Deletion of APOE4 in neutrophils reduced this immunosuppressive phenotype and restored microglial response to neurodegeneration (MGnD), limiting plaque pathology in AD mice. Mechanistically, IL-17F upregulated in APOE4 neutrophils interacts with microglial IL-17RA to suppress the induction of MGnD phenotype, and blocking this axis supported cognitive improvement in AD mice. These findings provide a translational basis to target IL-17F in APOE e4 female carriers with cognitive impairment.
2024-06-04 | GSE262632 | GEO
Project description:APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in females. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry, and validation in two independent cohorts of APOE4 female AD patients, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment. This phenotype is defined by increased IL-17 and IL-1 co-expressed gene modules in blood neutrophils and in microglia of cognitively impaired female APOE e4 carriers, showing increased infiltration to the AD brain. APOE4 female IL-17+ neutrophils upregulated the immunosuppressive cytokines IL-10 and TGFB and immune checkpoints, including LAG-3 and PD-1, associated with accelerated immune aging. Deletion of APOE4 in neutrophils reduced this immunosuppressive phenotype and restored the microglial response to neurodegeneration (MGnD), limiting plaque pathology in AD mice. Mechanistically, IL-17F upregulated in APOE4 neutrophils interacts with microglial IL-17RA to suppress the induction of MGnD phenotype, and blocking this axis supported cognitive improvement in AD mice. These findings provide a translational basis to target IL-17F in APOE e4 female carriers with cognitive impairment.
2024-06-04 | GSE260461 | GEO
Project description:Neutrophils are the most abundant nucleated cell type in the bone marrow. A pro-tumor bias in this cell type may have implications for bone-marrow residing malignancies, such as multiple myeloma. Here, we generated single cell transcriptomic overviews of the entire myeloid compartment, including the entire neutrophilic lineage, of the bone marrow of 6 newly diagnosed myeloma patients, 5 treated myeloma patients and 4 non-cancer controls. We find dat mature neutrophils in myeloma patients, both newly diagnosed and treated, have an activated and pro-inflammatory phenotype, accompanied by increased transcription of pro-inflammatory cytokines, such as IL-1β, and myeloma cell survival factors, such as BCMA-ligand BAFF/TNFSF13B. Moreover, inflammatory stromal cells can activate naive neutrophils to acquire an inflammatory phenotype as is seen in patients. Previously, we have shown that inflammatory stromal cells characterized the bone marrow of newly diagnosed myeloma patients. Here, we generate single cell RNA sequencing dataset of non-hematopoietic bone marrow cells of patients after induction treatment, high-dose melphalan, stem cell transplantation and consolidation treatment. We show that this intensive treatment reduced, but did not normalize, stromal inflammation.
2023-03-31 | E-MTAB-12760 | biostudies-arrayexpress
Project description:Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8 T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8 T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce reactive oxygen species and ultimately increased the hypoxic state and granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.
2024-04-29 | GSE193005 | GEO
Project description:This experiment was designed to compare the RNA expression profile in resting (control) neutrophils vs. that of TENs (neutrophils purified from tumor-bearing mice). In addition, we also compared the expression profiles of cultured neutrophils in vitro and treated with CCL2, CCL5 and GCSF. Circulating neutrophils were purified from control and 4T1 tumor-bearing mice and flash frozen. For in vitro cultures, circulating neutrophils were purified from control mice, cultured in the presence of chemokines for 2 hours and flash frozen.
2011-07-24 | E-GEOD-30887 | biostudies-arrayexpress