Project description:We performed RNAseq to identify miRNAs that were specifically down regulated in neutrophils, and RNAseq for identification of mRNA targets of miRNA-199 in neutrophils
Project description:We performed RNAseq to identify miRNAs that were specifically down regulated in neutrophils, and RNAseq for identification of mRNA targets of miRNA-99 in neutrophils
Project description:We performed RNAseq to identify miRNAs that were specifically down regulated in neutrophils, and RNAseq for identification of mRNA targets of miRNA-31, miRNA-190 and miRNA-375 in neutrophils
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.
Project description:Isolating Neutrophils from mouse blood, we employed bulk RNAseq and DE gene expression analysis to determine pathways that are regulated downstream of LTBR in neutrophils.
Project description:Purpose: The goals of this study are to compare bulk RNAseq profiles of tissue neutrophils in germ free mice. Methods: Bulk RNAseq of sorted neutrophils from spleen, blood, lung from spf and germ free mice, using Illumina. The sequence reads that passed quality filters were analyzed at the gene level with RSEM.
Project description:We report that tumor-infiltrating neutrophils are significantly different from their bone marrow and circulating neutrophils counterparts. We generated a heatmap clustering of the differentially expressed genes between the neutrophils from the three compartments, and identified four distinct gene clusters. Notably, genes in cluster 1 were down-regulated in tumor neutrophils, and comprised of genes involved in the adaptive immune response (GO:0002250). By contrast, genes in cluster 4 were up-regulated in tumor neutrophils, and consisted of genes involved in chemokine-mediated signalling pathway (GO:0070098) and positive regulation of cellular metabolic process (GO:0031325). We observed several cellular metabolic processes were up-regulated, suggesting a change in the metabolic signature of neutrophils that infiltrate the tumor. In conclusion, the distinct metabolic signature led us to hypothesize that the pronounced glycolytic profile of tumor-infiltrating neutrophils mediates pro-tumoral activity and PDAC progression.
Project description:We found different expression between glycolytic enzymes and TCA pathway in bone marrow neutrophils following LPS treatment, using RNAseq. This enable us to uncover the important role of glycolysis in activated neutrophils and the effect of HIF-1alpha on this pathway