Gene expression of human peripheral blood granulocytes (neutrophils)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108894 | GEO | 2018/02/05
REPOSITORIES: GEO
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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
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Project description:Severe congenital neutropenia (SCN) is a rare disorder characterized by a maturation arrest of myeloid progenitor cells in the bone marrow and severe reduction in the amount of circulating neutrophils. Loss-of-function mutations in the CSF3R (the gene encoding the granulocyte colony-stimulating factor (G-CSF) receptor) have been reported in a handful of cases. We describe two novel pedigrees with moderate neutropenia. G-CSFR immunostaining was greatly reduced on patient neutrophils. G-CSF did not prolong neutrophil survival or enhanced reactive oxygen species generation, and STAT-3 phosphorylation was absent, while neutrophils did respond to granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite a lack of G-CSF signaling, morphology and cellular proteomics were normal. We suggest the major role of G-CSF is not in myeloid differentiation, but in generation of sufficient number of committed progenitor cells for neutrophil release and their survival during inflammation, which corresponds with G-CSFR expression in myeloid cell fractions from bone marrow of healthy individuals.
2020-09-25 | PXD018178 | Pride
Project description:Gene expression of human peripheral blood granulocytes (neutrophils)
| PRJNA429036 | ENA
Project description:Neutrophil gene transcription following lipopolysaccharide exposure. Microarray analysis of lipopolysaccharide-treated human neutrophils. Neutrophils respond to infection by degranulation, release of reactive oxygen intermediates, and secretion of chemokines and cytokines; however, activation of neutrophil transcriptional machinery has been little appreciated. Recent findings suggest that gene expression may represent an additional neutrophil function after exposure to lipopolysaccharide (LPS). We performed microarray gene expression analysis of 4,608 mostly nonredundant genes on LPS-stimulated human neutrophils. Analysis of three donors indicated some variability but also a high degree of reproducibility in gene expression. Twenty-eight verifiable, distinct genes were induced by 4 h of LPS treatment, and 13 genes were repressed. Genes other than cytokines and chemokines are regulated; interestingly, genes involved in cell growth regulation and survival, transcriptional regulation, and interferon response are among those induced, whereas genes involved in cytoskeletal regulation are predominantly repressed. In addition, we identified monocyte chemoattractant protein-1 as a novel LPS-regulated chemokine in neutrophils. Included in these lists are five clones with no defined function. These data suggest molecular mechanisms by which neutrophils respond to infection and indicate that the transcriptional potential of neutrophils is greater than previously thought.
2010-06-05 | E-GEOD-105 | biostudies-arrayexpress
Project description:Neutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial co-infection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy subjects. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. Viability of neutrophils following co-culture with either pandemic and seasonal H1N1 IAV was similar for up to 18 h of culture. Notably, neutrophil exposure to seasonal IAV (but not pandemic IAV) primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest some strains of IAV prime neutrophils for enhanced bacterial clearance.
2017-12-05 | GSE100865 | GEO
Project description:Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.
2023-12-01 | GSE213770 | GEO
Project description:Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.
2023-12-01 | GSE213769 | GEO
Project description:Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.
2023-06-05 | GSE228077 | GEO
Project description:Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.
2023-12-01 | GSE213768 | GEO