A5066198455- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Immune cells in cancer
- NF-κB Signaling Pathways
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Adipose Tissue and Metabolism
- T-cell and B-cell Immunology
- Multiple Sclerosis Research Studies
- Antimicrobial Peptides and Activities
- TGF-β signaling in diseases
- Exercise and Physiological Responses
- Inflammatory Biomarkers in Disease Prognosis
- Gastrointestinal disorders and treatments
- Biliary and Gastrointestinal Fistulas
- Inflammasome and immune disorders
- Aortic aneurysm repair treatments
- Protein Tyrosine Phosphatases
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Melanoma and MAPK Pathways
- Inflammatory mediators and NSAID effects
- Systemic Lupus Erythematosus Research
Amsterdam University Medical Centers
2018-2023
University of Amsterdam
2014-2023
Amsterdam UMC Location University of Amsterdam
2014-2019
Technische Universität Dresden
2014
Saudi Arabia Basic Industries (Netherlands)
2014
Maastricht University
2012
Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression. The authors recently identified small molecule inhibitors that block interaction between CD40 and tumor necrosis factor receptor-associated (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity.This study evaluates potential of TRAF-STOP treatment atherosclerosis.The effects TRAF-STOPs on atherosclerosis were investigated...
Background: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of has only been implied through pharmacological intervention, in particular, because the somatic deletion CXCR4 gene mice is embryonically lethal. Moreover, cell-specific effects arterial wall underlying mechanisms remain elusive, prompting us to investigate relevance vascular types for atheroprotection. Methods: We examined atherosclerosis...
Significance Inflammation is a critical contributor to the pathogenesis of metabolic disorders associated with obesity. A group molecules crucial in regulating immune system are costimulatory molecules, including CD40. Our current study shows that CD40 acts as double-edged sword syndrome through initiation differential signaling cascades. The CD40-TNF receptor-associated factor (TRAF) 2/3/5 pathway protects against dysfunction and inflammation obesity; conversely, CD40-TRAF6 contributes...
Immunotherapy has revolutionized cancer treatment. However, immune checkpoint inhibitors (ICIs) that target PD-1 (programmed cell death protein-1) and/or CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) are commonly associated with acute immune-related adverse events. Accumulating evidence also suggests ICIs aggravate existing inflammatory diseases.As inflammation drives atherosclerotic cardiovascular disease, we studied the propensity of short-term ICI therapy to atherosclerosis.We used...
Abstract Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on cell-cell interactions involved, we sought to investigate function most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with CD40L-deficiency CD4 + display impaired Th1...
Obesity is associated with chronic low-grade inflammation, characterized by leukocytosis and inflammation in the adipose tissue. Continuous activation of immune system a stressor for hematopoietic stem progenitor cells (HSPCs) bone marrow (BM). Here we studied how diet-induced obesity (DIO) affects HSPC population dynamics BM. Eight groups age-matched C57Bl/6 mice received high-fat diet (45% kilocalories from fat) ranging 1 d up to 18 wk. The obesogenic caused decreased proliferation...
T cell-driven inflammation plays a critical role in the initiation and progression of atherosclerosis. The co-inhibitory protein Cytotoxic T-Lymphocyte Associated (CTLA) 4 is an important negative regulator cell activation. Here, we studied effects antibody-mediated inhibition CTLA4 on experimental atherosclerosis by treating 6-8-week-old Ldlr-/- mice, fed 0.15% cholesterol diet for six weeks, biweekly with 200 μg antibodies or isotype control weeks. 18F-fluorodeoxyglucose Positron Emission...
The E3-ligase CBL-B (Casitas B-cell lymphoma-B) is an important negative regulator of T cell activation that also expressed in macrophages. cells and macrophages mediate atherosclerosis, but their regulation this disease remains largely unknown; thus, we studied the function atherogenesis.The expression human atherosclerotic plaques was lower advanced lesions compared with initial correlated inversely necrotic core area. Twenty weeks old Cblb-/-Apoe-/- mice showed a significant increase...
Abstract Aims GITR—a co-stimulatory immune checkpoint protein—is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation autoimmunity, we investigated the relevance GITR in cardiovascular disease (CVD). Methods results expression was elevated carotid endarterectomy specimens obtained from patients with cerebrovascular events (n = 100) compared to asymptomatic 93) correlated parameters plaque vulnerability, including...
The influx of leukocytes into the central nervous system (CNS) is a key hallmark chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches combat MS. As CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells induce inflammation and trafficking, we explored hypothesis specific inhibition CD40-TRAF6 interactions can...
The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration aortic wall, we studied role costimulatory molecule CD40L, major driver inflammation, in aneurysm formation.Transcriptomics data obtained from human abdominal and normal aortas revealed increased abundance both CD40L CD40 media thrombus-free thrombus-covered samples. To further unravel formation, apolipoprotein E-deficient...
The costimulatory CD40L-CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII
Brown adipose tissue (BAT) activation and white (WAT) beiging can increase energy expenditure have the potential to reduce obesity associated diseases. The immune system is a target in mediating brown beige adipocyte activation. Type 2 anti-inflammatory cells contribute metabolic homeostasis within lean WAT, with prominent role for eosinophils interleukin (IL)-4-induced macrophages. We determined eosinophil numbers epididymal WAT (EpAT), subcutaneous (ScAT) BAT after 1 day, 3 days or week of...
A 66-year-old woman with abdominal pain and jaundice reported to our emergency department. An ultrasound examination revealed hepatic metastases distension of the common bile duct, indicating a primary malignancy pancreas or ducts. After an unsuccessful attempt restore outflow via stenting, second endoscopic retrograde cholangiopancreatography (ERCP) was conducted. During this procedure, stenosis left ducts observed, raising suspicion Therefore, 15-cm-long endoprosthesis inserted in secure...
Atherosclerosis is the underlying cause of many cardiovascular diseases, such as myocardial infarction or stroke. B cells, and their production pro- anti-atherogenic antibodies, play an important role in atherosclerosis. In TRAF2 NCK-interacting Kinase (TNIK), a germinal center kinase, was shown to bind TNF-receptor associated factor 6 (TRAF6), be involved JNK NF-κB signaling human pathway with antibody production. We here investigate TNIK-deficient cells ApoE-/-TNIKfl/fl (TNIKBWT)...