A5001121534- Immune cells in cancer
- Epigenetics and DNA Methylation
- Atherosclerosis and Cardiovascular Diseases
- Phagocytosis and Immune Regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cholesterol and Lipid Metabolism
- Macrophage Migration Inhibitory Factor
- Cell Adhesion Molecules Research
- Psoriasis: Treatment and Pathogenesis
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Immunotherapy and Immune Responses
- Cardiovascular Disease and Adiposity
- Sodium Intake and Health
- Nuclear Receptors and Signaling
- Chemokine receptors and signaling
- Cancer, Lipids, and Metabolism
- Regulation of Appetite and Obesity
University of Amsterdam
2015-2023
Amsterdam University Medical Centers
2018-2023
Amsterdam UMC Location University of Amsterdam
2015-2016
Highlights•Mouse and human M1 macrophages fail to repolarize M2 upon IL-4 restimulation•LPS + IFNγ treatment inhibits mitochondrial oxidative respiration in macrophages•Mitochondrial function is required for the repolarization an phenotype•NO blunts prevents plasticity macrophagesSummaryMacrophages are innate immune cells that adopt diverse activation states response their microenvironment. Editing macrophage dampen inflammatory diseases by promoting of (M1) anti-inflammatory (M2) high...
Specific metabolic pathways are increasingly being recognized as critical hallmarks of macrophage subsets. While LPS-induced classically activated M1 or M(LPS) macrophages pro-inflammatory, IL-4 induces alternative activation and these so-called M2 M(IL-4) support resolution inflammation wound healing. Recent evidence shows the crucial role reprogramming in regulation polarization. In this manuscript, an extracellular flux analyzer is applied to assess characteristics naive, polarized mouse...
Metabolic reprogramming has emerged as a crucial regulator of immune cell activation, but how systemic metabolism influences and function remains to be investigated. To investigate the effect dyslipidemia on metabolism, we performed in-depth transcriptional, metabolic, functional characterization macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage attenuate inflammatory responses. In addition diminished maximal mitochondrial...
Abstract Macrophages represent a major immune cell population in atherosclerotic plaques and play central role the progression of this lipid-driven chronic inflammatory disease. Targeting immunometabolism is proposed as strategy to revert aberrant macrophage activation improve disease outcome. Here, we show ATP citrate lyase (Acly) be activated macrophages human plaques. We demonstrate that myeloid Acly deficiency induces stable plaque phenotype characterized by increased collagen deposition...
T helper (Th) cells are CD4 + effector that play a critical role in immunity by shaping the inflammatory cytokine environment variety of physiological and pathological situations. Using combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A KDM6B as central regulators human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels repressive H3K27me3 chromatin mark leads to suppression key transcription factor RORγt during Th17 differentiation. In...
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...
Specific metabolic pathways are increasingly being recognized as critical hallmarks of macrophage subsets. While LPS-induced classically activated M1 or M(LPS) macrophages pro-inflammatory, IL-4 induces alternative activation and these so-called M2 M(IL-4) support resolution inflammation wound healing. Recent evidence shows the crucial role reprogramming in regulation polarization. In this manuscript, an extracellular flux analyzer is applied to assess characteristics naive, polarized mouse...
Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome many inflammatory diseases. Recent studies demonstrate activity particular chromatin-modifying is regulated by availability specific metabolites like acetyl-coenzyme A, S-adenosylmethionine, α-ketoglutarate, nicotinamide adenine dinucleotide and polyamines. In this way could sense macrophage's metabolic status translate into gene expression phenotypic changes. Importantly,...
Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether can induce proinflammatory priming of monocytes macrophages humans. We investigated effects on vitro vivo by performing randomized crossover trial which 11 healthy human subjects adhered to 2-week low-salt high-salt diet. demonstrate that increases monocyte expression CCR2, chemokine receptor mediates infiltration inflammatory diseases. In line with this, we show...
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...
Macrophages are highly plastic, key regulators of inflammation. Deregulation macrophage activation can lead to excessive inflammation as seen in inflammatory disorders like atherosclerosis, obesity, multiple sclerosis and sepsis. Targeting intracellular metabolism is considered an approach reshape deranged dampen the progression disorders. ATP citrate lyase (Acly) a metabolic enzyme important regulator activation. Using macrophage-specific Acly-deficient mouse model, we investigated role...
Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the main underlying cause cardiovascular disease. Here, we detailed effects hyperlipidemia on cells.In vitro, exposure human murine CD4+ cells to very low-density lipoprotein (VLDL), but not (LDL) resulted in upregulation Th1 associated pathways. VLDL was taken up via a CD36-dependent pathway membrane stiffening reduction lipid rafts. To further detail this response vivo, mice lacking LDL receptor (LDLr),...
Cancer cells rely on ATP-citrate lyase (Acly)-derived acetyl-CoA for lipid biogenesis and proliferation, marking Acly as a promising therapeutic target. However, inhibitors may have side effects tumor-associated macrophages (TAMs). TAMs are innate immune abundant in the tumor microenvironment (TME) play central roles tumorigenesis, progression therapy response. Since macrophage deletion was previously shown to elicit with increased pro- decreased anti-inflammatory responses vitro, we...
T helper (Th) cells are CD4+ effector that play an instrumental role in immunity by shaping the inflammatory cytokine environment a variety of physiological and pathological situations. Using combined chemico-genetic approach we identify histone H3K27 demethylases KDM6A KDM6B as central regulators human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels repressive H3K27me3 chromatin mark leads to suppression key transcription factor RORγt during Th17...