A5085087884- Systemic Sclerosis and Related Diseases
- Mast cells and histamine
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Dermatologic Treatments and Research
- Connective Tissue Growth Factor Research
- IL-33, ST2, and ILC Pathways
- Systemic Lupus Erythematosus Research
- Autoimmune Bullous Skin Diseases
- Inflammatory Myopathies and Dermatomyositis
- Bone and Dental Protein Studies
- Lymphatic System and Diseases
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Axon Guidance and Neuronal Signaling
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Salivary Gland Disorders and Functions
- Mesenchymal stem cell research
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Cancer Diagnosis and Treatment
- Skin and Cellular Biology Research
- Biomarkers in Disease Mechanisms
- Eosinophilic Disorders and Syndromes
Utrecht University
2017-2024
University Medical Center Utrecht
2015-2024
Heidelberg University
2015
University Hospital Heidelberg
2015
Institut Cochin
2012
Fibrosis is a major cause of mortality worldwide, characterized by myofibroblast activation and excessive extracellular matrix deposition. Systemic sclerosis prototypic fibrotic disease in which CXCL4 increased strongly correlates with skin lung fibrosis. Here we aim to elucidate the role fibrosis development. levels are multiple inflammatory mouse models, and, using CXCL4-deficient mice, demonstrate essential promoting events skin, lungs, heart. Overexpressing human mice aggravates, whereas...
MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature serum of systemic sclerosis (SSc) patients further assessed their expression early stages disease.The levels 758 miRNAs were evaluated 26 SSc compared to 9 healthy controls by using an Openarray platform. Three examined additional cohort 107 24 donors single qPCR. MiR-483-5p was analysed with localized...
Plasmacytoid dendritic cells (PDCs) are a critical source of type I interferons (IFNs) that can contribute to the onset and maintenance autoimmunity. Molecular mechanisms leading PDC dysregulation persistent IFN signature largely unexplored, especially in patients with systemic sclerosis (SSc), disease which PDCs infiltrate fibrotic skin lesions produce higher levels IFNα than those healthy controls. This study was undertaken investigate potential microRNA (miRNA)-mediated epigenetic...
Inhibitory receptors are crucial immune regulators and essential to prevent exacerbated responses, thus contributing homeostasis. Leukocyte associated immunoglobulin like receptor 1 (LAIR-1) is an inhibitory which has collagen domain containing proteins as ligands. LAIR-1 broadly expressed on cells a large availability of ligands in both circulation tissues, implicating need for tight regulation this interaction. In the current study, we sought examine function monocyte, dendritic cell (DC)...
Fibrosis is a condition shared by numerous inflammatory diseases. Our incomplete understanding of the molecular mechanisms underlying fibrosis has severely hampered effective drug development. CXCL4 associated with onset and extent development in multiple fibrotic Here, we used monocyte-derived cells as model system to study effects exposure on dendritic cell integrating 65 longitudinal paired whole genome transcriptional methylation profiles. Using data-driven gene regulatory network...
CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether plays a direct role induction IL-17 production by human CD4+ T cells currently unclear. Here, we demonstrated that induced to secrete co-expressed IFN-γ IL-22, differentiated naïve become Th17-cytokine producing cells. In co-culture system with monocytes or myeloid dendritic cells, upon triggering superantigen. Moreover, when monocyte-derived were...
Dendritic cells (DCs) constantly sample peripheral tissues for antigens, which are subsequently ingested to derive peptides presentation T in lymph nodes. To do so, DCs have traverse many different with varying oxygen tensions. Additionally, often exposed low tensions tumors, where vascularization is lacking, as well inflammatory foci, rapidly consumed by during the respiratory burst. respond levels tailor immune responses such low-oxygen environments. In present study, we identified a...
SSc is an autoimmune disease characterized by inflammation, vascular injury and excessive fibrosis in multiple organs. Secreted protein acidic rich cysteine (SPARC) a matricellular glycoprotein that regulates processes involved pathology, such as inflammation fibrosis. In vivo vitro studies have implicated SPARC SSc, but it unclear if the pro-fibrotic effects of on fibroblasts are result intracellular signalling or fibroblast interactions with extracellular hampering further development...
22 Abstract 23 Systemic sclerosis (SSc) is a rare chronic disease of unknown pathogenesis characterized by fibrosis 24 the skin and internal organs, vascular alteration dysregulation immune system. In order 25 to better understand system its perturbations leading diseases, study 26 mechanisms regulating cellular metabolism has gained wide interest. Here we assessed 27 metabolical status plasma dendritic cells (DCs) in patients with SSc. We identified 28 dysregulated metabolomic signature...
Systemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy and fibrosis in skin internal organs. Type I interferon signature found SSc propelled us to study plasmacytoid dendritic cells (pDCs) this disease. We aimed identify candidate pathways underlying pDC aberrancies validate its function on biology.In total, 1193 patients were compared 1387 healthy donors 8 localised scleroderma. PCR-based transcription factor profiling...
Objective To analyze the potential role of semaphorin 4A (Sema4A) in inflammatory and fibrotic processes involved pathology systemic sclerosis ( SS c). Methods Sema4A levels plasma healthy controls (n = 11) c patients 20) were determined by enzyme‐linked immunosorbent assay ELISA ). The expression its receptors monocytes CD 4+ T cells from 6–7 per group) was flow cytometry. Th17 cytokine production 5–7) analyzed mediators extracellular matrix ECM ) components dermal fibroblast 6)...
SSc is a complex disease characterized by vascular abnormalities and inflammation culminating in hypoxia excessive fibrosis. Previously, we identified chemokine (C-X-C motif) ligand 4 (CXCL4) as novel predictive biomarker SSc. Although CXCL4 well-studied, the mechanisms driving its production are unclear. The aim of this study was to elucidate leading production.Plasmacytoid dendritic cells (pDCs) from 97 healthy controls 70 patients were cultured presence or atmospheric oxygen level and/or...
Angiopoietin-2 (Ang-2), a ligand of the tyrosine kinase receptor Tie2, is essential for vascular development and blood vessel stability also involved in monocyte activation. Here, we examined role Ang-2 on activation patients with systemic sclerosis (SSc). levels were measured serum skin healthy controls (HCs) SSc by ELISA array profiling, respectively. mRNA expression ANG2 was analyzed monocytes, dermal fibroblasts, human pulmonary arterial endothelial cells (HPAECs) quantitative PCR....
Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts extracellular matrix components such as collagen interferes with organ function. LAIR-1 an inhibitory receptor highly expressed on tissue immune cells. We questioned whether SSc, impaired LAIR-1-collagen interaction contributing to ongoing inflammation and fibrosis. found that SSc patients do not have intrinsic defect expression or Instead, fibroblasts from healthy controls...
Abstract Fibrosis is a condition shared by numerous inflammatory diseases. Our incomplete understanding of the molecular mechanisms underlying fibrosis has severely hampered effective drug development. CXCL4 associated with onset and extent development in systemic sclerosis, prototypic fibrotic disease. Here, we integrated 65 paired longitudinal transcriptional methylation profiles from monocyte-derived cells with/without exposure. Using data-driven gene regulatory network analyses,...
<h3>Background</h3> CXCL4 regulates multiple facets of immune response and its level is highly increased in various Th17-associated rheumatic diseases, including systemic sclerosis (SSc)<sup>1–4</sup>. Recently, was shown to induce type I interferon production as well endothelial activation SSc patients<sup>1</sup>. Th17 skewing has been demonstrated SSc<sup>5–6</sup>, however, whether plays a role the induction IL-17 by human CD4 T cells currently unclear. <h3>Objectives</h3> To investigate...
Abstract Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts extracellular matrix components such as collagen interferes with organ function. LAIR-1 an inhibitory receptor highly expressed on tissue immune cells. We questioned whether SSc, impaired LAIR-1-collagen interaction contributing to ongoing inflammation and fibrosis. found that SSc patients do not have intrinsic defect expression or Instead, fibroblasts from deposit...
<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, vascular injury and excessive fibrosis in different organs. Different studies have shown that Th17 cells cytokines (IL-17, IL-21 IL-22) play a key role the pathogenesis of disease. Semaphorin 4A (Sema4A) transmembrane protein belongs to large family proteins initially described as ligands essential for neuronal development. Further they also other biological processes including control immune...