Single-cell RNA sequencing of healthy and inflamed murine neutrophils
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE165276 | GEO | 2021/02/10
REPOSITORIES: GEO
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Project description:Single cell transcriptomes of flow cytometry-sorted peripheral blood NK cells from COVID-19 patients and healthy controls. Single cell transcriptomes of peripheral blood NK cells from healthy donors stimulated with IL-12 and IL-15 +/- TGF-beta.
2021-10-25 | GSE184329 | GEO
Project description:TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production. In this dataset, expression data of genes induced by septic peritonitis in spleens from TLR-deficient and wildtype mice are included. 3 groups (septic TLR-deficient mice, septic wildtype mice, and untreated wildtype mice) with 4 replicates each.
2011-06-27 | E-GEOD-24327 | biostudies-arrayexpress
Project description:Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5’ RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFb and TNFa/NFkB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells – reflecting this disease’s unique inflammatory T-cell driven nature – as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
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Project description:Palmer2014 - Effect of IL-1β-Blocking therapies in T2DM - Healthy Condition
This is the model with healthy state initial conditions. A few changes were made to the model equations in order to bypass the circular dependencies apparent in SBML. Coupled algebraic equations for the species Glucose, Insulin and Proinsulin were changed to reactions which represent the ordinary differential equations found in a previously published model by De Gaetano
et al (2008), [MODEL1112110003]. This reference was used by the present authors for the algebraic equations. The original Mathematica code, obtained from the supplementary material of the article can be downloaded from the link below:
[Palmer2014_notebook.nb].
This model is described in the article:
Effects of IL-1β-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms.
Palmér R, Nyman E, Penney M, Marley A, Cedersund G, Agoram B.
CPT Pharmacometrics Syst Pharmacol. 2014 Jun 11;3:e118.
Abstract:
Recent clinical studies suggest sustained treatment effects of interleukin-1β (IL-1β)-blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL-1β effects on β-cell function and turnover with a disease progression model of the long-term interactions between insulin, glucose, and β-cell mass in type 2 diabetes mellitus. We then simulated treatment effects of the IL-1 receptor antagonist anakinra. The result was a substantial and partly sustained symptomatic improvement in β-cell function, and hence also in HbA1C, fasting plasma glucose, and proinsulin-insulin ratio, and a small increase in β-cell mass. We propose that improved β-cell function, rather than mass, is likely to explain the main IL-1β-blocking effects seen in current clinical data, but that improved β-cell mass might result in disease-modifying effects not clearly distinguishable until >1 year after treatment.
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2024-09-02 | BIOMD0000000621 | BioModels
Project description:TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production.
2011-06-28 | GSE24327 | GEO
Project description:Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. Human healthy EPCs from bone marrow were isolated and cultured under proangiogenic stimulation; after IFNa incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.
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Project description:Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. This SuperSeries is composed of the SubSeries listed below. Human healthy and lupus EPCs and CACs from PBMCs, and healthy EPCs from bone marrow, were isolated and cultured under proangiogenic stimulation; after IFN-α incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.
2011-04-13 | E-GEOD-23203 | biostudies-arrayexpress
Project description:The purpose of the experiment was to transcriptionally characterize transgenic T cells derived from cord blood (CB) and cultured with IL-2 or IL-7 and IL-15, or from peripheral blood (PB) and cultured with IL-2. The sample replicates were generated using peripheral and cord blood mononuclear cells, obtained from healthy human donors and cord blood units that were not compliant with banking standards, respectively. T cells were then transduced with a retroviral vector encoding an HLA-DRB1*04-restricted TCR targeting the human papillomavirus oncoprotein E7.
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Project description:Human CD71+ erythroid cells (CECs) have been recognized to have an immunoregulatory function via direct cell-cell interaction and soluble mediators such as arginase-2 and reactive oxygen species. Circulating CECs increase in healthy newborns or patients with hemolytic, malignant and cardiopulmonary disorders. To assess the pathophysiological role of CECs in inflammatory diseases, we studied the gene expression and function focusing on systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells obtained from patients with SoJIA expressed upregulated erythropoiesis-related genes, that determined the largest increase of circulating CECs during active phase SoJIA of all inflammatory diseases including polyarthritis, Kawasaki disease, bacteremia and systemic lupus erythematosus. Despite the opposite roles of erythropoietin and hepcidin in erythropoiesis, both serum levels positively correlated with the amounts of peripheral blood CECs in SoJIA patients. There were positive correlations between CECs and inflammatory markers of C-reactive protein, interleukin (IL)-6, IL-18, or soluble TNF receptor. Co-culture with active SoJIA-driven CECs significantly suppressed the secretion of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top of upregulated genes in SoJIA-driven CECs was ARG2 compared with those in CECs from cord blood controls. On the other hand, cytokine productions from monocytes were suppressed by co-culture even with an arginase inhibitor. CECs are mobilized to periphery in SoJIA for the control of excessive inflammation via the immuno-regulatory pathways partly involving arginase-2. Understanding the association between CECs and magnitude of systemic inflammation may clarify the unappreciated role of erythroid precursors in health and disease process of immune dysregulation.
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