A5011553962- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
- Advanced Glycation End Products research
- Systemic Lupus Erythematosus Research
- Adipokines, Inflammation, and Metabolic Diseases
- Chemokine receptors and signaling
- Immune cells in cancer
- Pregnancy and preeclampsia studies
- Biomarkers in Disease Mechanisms
- Reproductive System and Pregnancy
- Maternal and fetal healthcare
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- Inflammasome and immune disorders
- Complement system in diseases
- Lipoproteins and Cardiovascular Health
- Head and Neck Cancer Studies
- Kruppel-like factors research
- Cancer-related molecular mechanisms research
- Cell death mechanisms and regulation
University of Birmingham
2023-2024
Queen Elizabeth Hospital Birmingham
2022
St George's, University of London
2012-2021
St George’s University Hospitals NHS Foundation Trust
2020-2021
Fondation pour l’innovation en Cadiométabolisme et Nutrition
2016
Erasmus MC
2016
Inserm
2016
Sorbonne Université
2016
Medical Research Council
2008-2015
South West London and St George's Mental Health NHS Trust
2012
Abstract High mobility group box 1 (HMGB1) is an abundant and conserved nuclear protein that released by necrotic cells acts in the extracellular environment as a primary proinflammatory signal. In this study we show human dendritic cells, which are specialized Ag presentation to T actively release their own HMGB1 into milieu upon activation. This secreted necessary for up-regulation of CD80, CD83, CD86 surface markers IL-12 production. The also required clonal expansion, survival,...
Chemokines regulate the migration and maturation of dendritic cells (DC) licensed by microbial constituents. We have recently found that function DC, including their ability to activate naïve, allogeneic CD4+ T cells, requires autocrine/paracrine release nuclear protein high mobility group box 1 (HMGB1). show here human myeloid which rapidly secrete upon induction own HMGB1, remodel actin-based cytoskeleton, up-regulate CCR7 CXCR4 chemokine receptors, acquire migrate in response receptor...
Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) a specialized subset that produce high amounts type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as potent pro-inflammatory factor when released extracellularly. We show HMGB1 leaves the nucleus maturing PDC following TLR9 activation, express on plasma membrane best-characterized receptor for HMGB1, RAGE....
Abstract Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present tumor milieu can alter maturation DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human increased TGF-β1 transcripts following culture with lung carcinoma (LCCs). These produced amounts protein compared not exposed LCCs also decreased CD86 HLA-DR by immature DCs. Furthermore, production TNF-α IL-12...
Rationale: Patients with acute coronary syndrome (ACS) predisposed to recurrent events have an expansion of a distinctive T-cell subset, the CD4 + CD28 null T cells. These cells are highly inflammatory and cytotoxic in spite lacking costimulatory receptor CD28, which is crucial for optimal cell function. The mechanisms that govern function unknown. Objective: Our aim was investigate expression role alternative receptors ACS. Methods Results: Expression (inducible costimulator, OX40, 4–1BB,...
BackgroundCells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses promote trophic signaling pathways. Paradoxically, because of potential cause death tumor thereby militate against malignant disease progression, both tumor-associated macrophages (TAMs) often associated with poor prognosis in cancer. We hypothesized that, progression disease, constitutive...
Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds high affinity phosphatidylserine on surface apoptotic and necrotic thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets CD8+ dendritic for in vivo clearance, elicits release proinflammatory cytokines dramatically enhances...
Abstract Pentraxins (PTX) and complement belong to the humoral arm of innate immune system have essential functions in defense microbes scavenging cellular debris. The prototypic long PTX, PTX3, first component classical pathway, C1q, are opsonins involved disposal dying cells by phagocytes. Whether interaction between various impacts on their function is not fully understood. We show here that characterized Toll-like receptor (TLR) ligands elicit production C1q PTX3 immature dendritic (DC)....
Dendritic cells (DCs) are known to produce C1q, the initiator of classical complement pathway. We demonstrate that murine DCs deficient in C1q (C1qa(-/-)) poorer than wild-type (WT) at eliciting proliferation and Th1 differentiation antigen-specific T cells. These defects result from decreased production IL-12p70 by C1qa(-/-) impaired expression costimulatory molecules CD80 CD86 response CD40 ligation. The defective reduced were specifically mediated via ligation, as normal levels CD80/86...
The number of CD4(+)CD28(null) (CD28(null)) T cells, a unique subset lymphocytes with proinflammatory and cell-lytic phenotype, increases markedly in patients acute coronary syndrome (ACS). ACS harboring high numbers CD28(null) cells have increased risk recurrent severe events unfavorable prognosis. mechanisms that govern the increase remain elusive. We investigated whether apoptosis pathways regulating T-cell homeostasis are perturbed ACS.We found were resistant to induction via...
Background: The co-inhibitory receptor PD-1 is expressed in many tumours including head and neck squamous cell carcinoma (HNSCC) an important immunotherapy target. However, the role of ligands, PD-L1 particularly PD-L2, tumour-stromal interactions that cause a tumour-permissive environment HNSCC not completely understood focus our study. Methods: Expression PD-L2 was analysed by immunohistochemistry situ tumour tissue. Co-cultures were established between stromal cells (fibroblasts...
Head and neck cancers (HNC) are aggressive tumours. Overexpression of p16 in HNC correlates with human papilloma virus (HPV)-associated that carry a better prognosis than HPV-negative Angiogenesis is an important factor tumour progression. Our aim was to dissect the impact expression on angiogenesis factors HNC. Eighteen newly diagnosed patients controls were analysed. Eleven pro- anti-angiogenesis quantified using multiplex ELISA controls. analysed tissue immunohistochemistry. Circulating...
Inflammation has important roles in atherosclerosis. CD4+CD28null (CD28null) T cells are a specialized lymphocyte subset that produce inflammatory cytokines and cytotoxic molecules. CD28null expand preferentially patients with acute coronary syndrome (ACS) rather than stable angina barely detectable healthy subjects. Importantly, ACS T-cell expansion have increased risk for recurrent events poor prognosis, compared to whom this cell does not expand. The mechanisms regulating remain elusive....