A5078989507- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Multiple Sclerosis Research Studies
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- PARP inhibition in cancer therapy
- Adipose Tissue and Metabolism
- Nutritional Studies and Diet
- Liver Disease Diagnosis and Treatment
- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Sirtuins and Resveratrol in Medicine
- MicroRNA in disease regulation
- Invertebrate Immune Response Mechanisms
- Calcium signaling and nucleotide metabolism
- Immune cells in cancer
University of Amsterdam
2017-2022
Amsterdam University Medical Centers
2018-2022
Amsterdam UMC Location University of Amsterdam
2017-2018
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...
Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. We aimed to investigate the of 6 wk supplementation on insulin sensitivity, mitochondrial function, and other parameters in overweight obese volunteers. A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted 13 healthy or men women. Participants received (1000 mg/d) placebo...
Abstract Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis induces favourable stable phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function myeloid using myeloid-specific CD40-deficient...
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 co-stimulatory CD40-CD40L dyad plays a central role in fine-tuning immune reactions, including obesity-induced inflammation. Genetic ablation of CD40L reduced adipose tissue inflammation, while absence CD40 resulted aggravated metabolic dysfunction mice. During obesity, expressing CD11c+ dendritic cells (DC) and macrophages accumulate liver. We investigated the CD40+CD11c+ syndrome nonalcoholic steatohepatitis (NASH). DC-CD40-ko mice (CD40fl/flCD11ccre) were subjected to obesity or NASH....
The costimulatory CD40L-CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII
The co-stimulatory CD40-CD40L dyad plays an important role in chronic inflammatory diseases associated with aging. Although CD40 is mainly expressed by immune cells, also present on adipocytes. We aimed to delineate the of adipocyte aging hematopoietic system and evaluated effects deficiency cardiometabolic diseases. Adult CD40-deficient mice (AdiCD40KO) had a decrease bone marrow stem cells (Lin-Sca+cKit+, LSK) common lymphoid progenitors, which was increased adiposity T-cell activation,...
Objective Obesity-associated metabolic dysfunction increases the risk of multiple diseases such as type 2 diabetes and cardiovascular disease. The importance co-stimulatory CD40-CD40L dyad in diet-induced obesity (DIO), with opposing phenotypes arising when either receptor (aggravating) or ligand (protective) is deleted, has been described previously. functions CD40 CD40L are cell dependent. As co-stimulation via T cell-mediated essential for driving inflammation, we here investigate role...
Obesity is a low-grade inflammatory disease that increases the risk for metabolic disorders. CD40-CD40L signaling plays central role in obesity-induced inflammation. Genetic deficiency of CD40L diet-induced obesity (DIO) ameliorates adipose tissue inflammation, hepatic steatosis and insulin sensitivity. Unexpectedly, absence CD40 worsened resistance caused excessive inflammation hepatosteatosis. To investigate whether macrophage responsible phenotype observed CD40-/- mice, we generated...
Introduction: The co-stimulatory dyad CD40-CD40L plays a central role in fine-tuning immune reactions atherosclerosis, obesity-induced inflammation and multiple sclerosis (MS). Inhibition of CD40 atherosclerosis experimental autoimmune encephalomyelitis (EAE) ameliorates disease outcome, whereas CD40-deficiency diet induced obesity (DIO) model worsens insulin resistance induces excessive adipose tissue inflammation. Although inhibition has powerful effects, we do not know which expressing...