A5062882861- Lymphatic System and Diseases
- Immunotherapy and Immune Responses
- Lymphatic Disorders and Treatments
- Angiogenesis and VEGF in Cancer
- Streptococcal Infections and Treatments
- Proteoglycans and glycosaminoglycans research
- Neonatal Respiratory Health Research
- Ocular Surface and Contact Lens
- Cardiovascular Health and Disease Prevention
- T-cell and B-cell Immunology
- Sympathectomy and Hyperhidrosis Treatments
- Wound Healing and Treatments
- Genital Health and Disease
- Atherosclerosis and Cardiovascular Diseases
- Autoimmune and Inflammatory Disorders Research
- Diagnosis and Treatment of Venous Diseases
- Infections and bacterial resistance
- Pressure Ulcer Prevention and Management
- Central Venous Catheters and Hemodialysis
- Extracellular vesicles in disease
- Dermatological and COVID-19 studies
- IL-33, ST2, and ILC Pathways
- Dermatology and Skin Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Vascular Malformations and Hemangiomas
MRC Human Immunology Unit
2008-2022
University of Oxford
2008-2022
MRC Weatherall Institute of Molecular Medicine
2019-2022
John Radcliffe Hospital
2006-2022
Medical Research Council
2005-2021
Institute of Molecular Medicine
2018
Novo Nordisk (United Kingdom)
2005
Karolinska Institutet
2005
University of Hong Kong
2005
The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation maintenance dermal immune responses. How such an achieved how transmigrate distinct endothelium lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation endothelial (LECs), leading expression key leukocyte adhesion receptors intercellular molecule 1 (ICAM-1), vascular cell (VCAM-1), E-selectin, as well a discrete panel chemokines other potential...
Myocardial infarction (MI) arising from obstruction of the coronary circulation engenders massive cardiomyocyte loss and replacement by non-contractile scar tissue, leading to pathological remodeling, dysfunction, ultimately heart failure. This is presently a global health problem for which there no effective cure. Following MI, innate immune system directs phagocytosis dead cell debris in an effort stimulate repopulation tissue renewal. In mammalian adult heart, however, persistent influx...
Lymphangiogenesis is an important process that contributes to the spread of cancer. Here we show insulin-like growth factors 1 (IGF-1) and 2 (IGF-2) induce lymphangiogenesis in vivo . In a mouse cornea assay, IGF-1 IGF-2 as detected with LYVE-1, specific marker for lymphatic endothelium. Interestingly, IGF-1-induced could not be blocked by soluble vascular endothelial factor receptor 3, suggesting 3-signaling pathway required IGF-induced lymphangiogenesis. vitro , significantly stimulated...
Tissue inflammation induces rapid mobilization of antigen-charged dendritic cells (DCs), which migrate to draining lymph nodes via afferent lymphatics elicit the immune response. This increase in DC trafficking has been shown require integrin-dependent adhesion ICAM-1 and VCAM-1, expressed on inflamed lymphatic endothelium. In addition, both constitutive- inflammation-induced migration involves chemokine CCL21, most likely triggers integrin activation its receptor CCR7. Recently, however,...
The hyaluronan receptor LYVE-1 is selectively expressed in the endothelium of lymphatic capillaries, where it has been proposed to function clearance and hyaluronan-mediated leukocyte adhesion. However, recent studies suggest that homeostasis unperturbed LYVE-1(-/-) mice adhesion/transmigration may be largely mediated by ICAM-1 VCAM-1 rather than LYVE-1. Here we have explored possibility functions during inflammation report down-regulated pro-inflammatory cytokines. Using cultured primary...
We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and it mediates powerful platelet aggregation by snake venom toxin rhodocytin. In addition, we provided indirect evidence for an endogenous ligand CLEC-2 in renal cells expressing HIV-1. This putative facilitates transmission of HIV through its incorporation into viral envelope binding to platelets. The aim present study was identify these which binds Recombinant exhibits specific HEK-293T (human...
Tissue inflammation is characterised by increased trafficking of antigen-loaded dendritic cells (DCs) from the periphery via afferent lymphatics to draining lymph nodes, with a resulting stimulation ongoing immune responses. Transmigration across lymphatic endothelium constitutes first step in this process and known involve chemokine CCL21 its receptor CCR7. However, precise details DC transit remain obscure it likely that additional chemokine-receptor pairs have roles vessel entry. Here, we...
Neutrophils are the first leukocyte population to be recruited from circulation following tissue injury or infection, where they play key roles in host defense. However, recent evidence indicates neutrophils can also enter lymph and shape adaptive immune responses downstream draining nodes. At present, cellular mechanisms regulating neutrophil entry lymphatic vessels migration nodes largely unknown. Here, we have investigated these events an vivo mouse Mycobacterium bovis bacillus...
Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also basolateral exosome-rich vesicles (EEVs) are secreted in greater numbers presence inflammatory cytokines and accumulate perivascular stroma small lymphatic vessels human chronic diseases. Proteomic analyses EEV fractions identified >1,700 cargo proteins revealed a dominant motility-promoting protein signature. vitro ex vivo augmented cellular...
The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human group A streptococcus has a predilection to induce pathology in system and draining lymph nodes, however underlying basis subsequent consequences disease outcome are currently unknown. Here we report that hyaluronan capsule of streptococci is crucial virulence determinant tropism vivo, further, identify vessel endothelial receptor-1 as critical receptor capsular system....
Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack vessels escape local infection site, transiting sequential lymph nodes and efferent enter bloodstream. Contrasting with previously reported mechanisms intracellular pathogen carriage by phagocytes, show S. remain extracellular during transit, first in afferent then lymphatics carry bacteria successive draining...
Generating a protective immune response to viral infection is known depend upon the priming and clonal expansion of virus-specific CD8(+) T cells by Ag-loaded dendritic (DC) within secondary lymphoid tissue. However, actual initiation involves critical upstream events that control recruitment mature Ag-charged DC from periphery via afferent lymphatics, are still only partly understood. Recent evidence has revealed transmigration lymphatic endothelium regulated adhesion molecules ICAM-1...
DCs play a vital role in immunity by conveying antigens from peripheral tissues to draining lymph nodes, through afferent lymphatic vessels. Critical the process is initial docking endothelial receptor LYVE-1 via its ligand hyaluronan on DC surface. How this relatively weak binding polymer configured for specific adhesion LYVE-1, however, unknown. Here, we show that anchored and spatially organized into 400–500 nm dense glycocalyx leukocyte CD44. Using gene knockout modulating...
Lymphatic vessels carry fluid from tissues back to the bloodstream through filtering lymph nodes that limit infection and restrict passage of pathogens; ability exploit these conduits is ascribed only cancer cells a small number of, principally intracellular, pathogens. Here, we report Streptococcus pyogenes other extracellular bacteria rapidly escape local site enter blood circulation via lymphatics, passing sequential draining nodes, transiting in inter-nodal efferent lymphatic vessels,...