A5001326791- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- interferon and immune responses
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Immune Response and Inflammation
- Inflammatory Bowel Disease
- NF-κB Signaling Pathways
- Immune responses and vaccinations
- Vasculitis and related conditions
- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Adipokines, Inflammation, and Metabolic Diseases
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Chronic Lymphocytic Leukemia Research
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Mycobacterium research and diagnosis
University of Oxford
2017-2024
Kennedy Center
2018-2020
Institute of Rheumatology
2020
Imperial College London
2017
Queen Mary University of London
2017
Lund University
2017
Background: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity macrophages, promoting persistent proatherogenic characteristics. Methods: Bone marrow–derived macrophages from control mice and with were grown physiological glucose (5 mmol/L) subjected to RNA sequencing (n=6), assay for transposase accessible chromatin immunoprecipitation (n=6) determination of hyperglycemia-induced immunity. marrow...
Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes uptake apoptotic (efferocytosis) promotes growth establishment a necrotic core. The transcription factor interferon regulatory (IRF)-5 is an important modulator myeloid function programming. We sought investigate whether IRF5 affects the formation phenotype lesions.We investigated role in atherosclerosis 2 complementary models. First, hyperlipidemic...
Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators prognosis or treatment responses. We used single technologies to comprehensively map immune populations the blood patients GCA and identified CD66b+CD15+CD10lo/–CD64– band neutrophils CD66bhiCD15+CD10lo/–CD64+/bright myelocytes/metamyelocytes be unequivocally associated both clinical phenotype response treatment. Immature were resistant apoptosis, remained vasculature for...
Abstract Interferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, and has key pathogenic function in gut inflammation, but how IRF5 modulated still unclear. Having performed kinase inhibitor library screening macrophages, here we identify protein-tyrosine 2-beta (PTK2B/PYK2) as putative kinase. PYK2-deficient macrophages display impaired endogenous activation, leading to reduction inflammatory gene expression. Meanwhile, PYK2 inhibitor, defactinib, similar...
Improved knowledge of different biomarkers is crucial for early diagnosis rheumatic diseases and to provide important insights clinical management. In this study, we evaluated the seroreactivity patients with connective tissue (CTDs) (rheumatoid arthritis, RA; systemic lupus erythematosus, SLE; sclerosis, SSc; Sjogren's syndrome, SSj) interferon regulatory factor 5 (IRF5) peptide homologs derived from Epstein-Barr virus (EBV) Mycobacterium avium subsp. paratuberculosis (MAP). Antigen-induced...
Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage phenotype and key transcription involved in expression proinflammatory cytokine responses to microbial viral infection. Here, we show that IRF5 controls cellular metabolic responses. By integrating ChIP sequencing (ChIP-Seq) assay for transposase-accessible chromatin using (ATAC)-seq data sets, found directly regulates genes such as hexokinase-2 (Hk2). The interaction had functional consequence, Irf5
The PI3K pathway plays a key role in B cell activation and is important for the differentiation of Ab producing plasma cells (PCs). Although much known about molecular mechanisms that modulate signaling cells, transcriptional regulation expression poorly understood. In this study, we identify zinc finger protein Zbtb18 as repressor directly binds enhancer/promoter regions genes encoding class I regulatory subunits, subsequently limiting their expression, dampening suppressing PC responses....
During development neutrophils undergo extensive changes in nuclear morphology, gene expression programmes, and acquire specific effector functions. However, molecular mechanisms controlling neutrophil remain largely unknown. Here we systematically analysed chromatin landscape across stages of differentiation, to construct a network transcription factors, predicted control acquisition Zinc finger protein 263 (Zfp263) emerged at the apex this network. Neutrophil maturation ex vivo was blocked...
Abstract Mononuclear phagocytes (MNPs) play a key role in maintaining intestinal homeostasis but also triggering immunopathology response to acute microbial stimulation, which induces the recruitment of masses Ly6C hi monocytes gut. The regulators that control monocyte tissue adaptation gut remain poorly understood. Interferon Regulatory Factor 5 (IRF5) is transcription factor previously shown inflammatory phenotype macrophages. Here we investigate impact IRF5 on MNP system and physiology at...
<h3>Background</h3> The mechanisms by which diabetes increases atherosclerosis and cardiovascular disease risk even after glucose normalisation remains unknown. We hypothesised that: hyperglycaemia alters cellular metabolism; these changes drive pro–inflammatory responses, remain altered increase in vivo. <h3>Methods results</h3> Hyperglycaemia monocyte, macrophage hematopoietic stem cell (HSC) metabolism, significantly increasing glycolysis (FDR=0.02, human monocyte non-targeted...
Abstract Inflammatory bowel disease (IBD) is a group of inflammatory disorders the gastro-intestinal tract caused by complex combination genetic and environmental factors. Interferon regulating factor 5 (IRF5) multifunctional regulator immune responses, which plays key pathogenic role in mouse colitis models risk for IBD. A screen protein kinase inhibitor library macrophages revealed list putative IRF5 kinases. Among top hits validated multiple vitro assays, protein-tyrosine 2-beta (PTK2B or...