A5008274472- Systemic Sclerosis and Related Diseases
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Mast cells and histamine
- Systemic Lupus Erythematosus Research
- Lymphatic System and Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Spaceflight effects on biology
- Inflammatory Myopathies and Dermatomyositis
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Autoimmune Bullous Skin Diseases
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- IL-33, ST2, and ILC Pathways
- T-cell and Retrovirus Studies
- Cell Adhesion Molecules Research
- Nuclear Receptors and Signaling
- Eosinophilic Disorders and Syndromes
- Chemokine receptors and signaling
- Salivary Gland Disorders and Functions
- Dermatologic Treatments and Research
- Immune responses and vaccinations
- Connective Tissue Growth Factor Research
University Medical Center Utrecht
2017-2022
Utrecht University
2017-2022
University of Coimbra
2011-2014
Centro de Neurociências e Biologia Celular
2013
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...
Objective CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their role disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between activity and cell phenotypes, production of cytokines, cytotoxic molecules peripheral blood (PB) synovial fluid (SF) patients with RA. Methods phenotypes were determined 96 RA (44 remission, 34 active disease, 18 low activity) 64 sex‐ age‐matched healthy controls. Ten paired PB SF samples from analyzed....
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...
Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs 44 healty controls (HC) using mass-cytometry assessed diagnostic value results. Alterations immune-cell subsets were present all compared to HC. Most alterations, including a decrease CD56hi NK-cells SSc IgM+ Bcells pSS, disease...
Background and objective Systemic sclerosis (SSc) is a severe autoimmune disease, in which the pathogenesis dependent on both genetic epigenetic factors. Altered gene expression SSc monocytes, particularly of interferon (IFN)-responsive genes, suggests their involvement development. We investigated correlation between histone marks monocytes. Methods Chromatin immunoprecipitation followed by sequencing (ChIPseq) for H3K4me3 H3K27ac was performed monocytes nine healthy controls 14 patients...
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...
Abstract Chemokines have been shown to play immune-modulatory functions unrelated steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role dendritic cells (DCs) in activation, this article we addressed effect on phenotype function monocyte-derived DCs (moDCs). To end, compared innate adaptive responses...
Compelling evidence shows the involvement of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc) pathogenesis. This study investigated whether microRNAs (miRNAs) are involved dysregulation pDCs SSc patients already at early stages. RNA from circulating was isolated two independent cohorts with different disease phenotypes, and individuals Raynaud’s phenomenon, for microRNA profiling RNA-sequencing analysis. Proteomic analysis exploited to identify novel direct miRNA targets...
The T-cell receptor (TCR) is a highly polymorphic surface that allows T-cells to recognize antigenic peptides presented on the major histocompatibility complex (MHC). Changes in TCR repertoire have been observed several autoimmune conditions, and these changes are suggested predispose autoimmunity. Multiple lines of evidence implied an important role for pathogenesis Systemic Sclerosis (SSc), disease. One questions regarding roles whether expansion activation diseases antigen driven. To...
Interleukin (IL)-12 and IL-23 are pro-inflammatory cytokines produced by dendritic cells (DCs) associated with Psoriasis (Pso) Psoriatic Arthritis (PsA) pathogenesis. Tofacitinib, a Janus kinase inhibitor, effectively suppresses inflammatory cascades downstream the IL-12/IL-23 axis in Pso PsA patients. Here, we investigated whether Tofacitinib directly regulates production DCs, how this regulation reflects responses to We treated monocyte-derived myeloid stimulated either lipopolysaccharide...
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...
This study was undertaken to identify key disease pathways driving conventional dendritic cell (cDC) alterations in systemic sclerosis (SSc).Transcriptomic profiling performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 patients with SSc, including all major subtypes. We differential expression analysis for the different SSc subtypes uncover genes dysregulated SSc. To biologically relevant pathways, we built a gene coexpression network using weighted...
The chemokine CXCL4 has been implicated in several immune diseases. Exposure of monocyte-derived dendritic cells (moDCs) to potentiates the production inflammatory cytokines presence TLR3 or TLR7/8 agonists. Here we investigated transcriptional and post-transcriptional events underlying augmented responses CXCL4-moDCs. Our results indicate that CXCL4-moDCs display an increased expression secretion IL-12, IL-23, IL-6 TNF upon activation. Analysis cytokine transcripts for AU-rich elements...
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,...
ABSTRACT Objectives To identify key disease pathways driving conventional dendritic cell (cDC) alterations in Systemic Sclerosis (SSc). Methods Transcriptomic profiling was performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 SSc patients with all major subtypes. Differential expression analysis comparing the different subtypes to uncover genes dysregulated SSc. biologically relevant pathways, a gene co-expression network built using Weighted Gene...
<h3>Background and Objectives</h3> CD8<sup>+</sup>T cells are known to be present in the synovial fluid synovium of rheumatoid arthritis. However, their role disease pathogenesis remains largely unexplored. This work intended characterise blood cell functional subsets found patients with arthritis explore importance regulating activity disease. <h3>Methods</h3> The phenotypes were determined seventy-eight (forty-four remission (DAS28 < 2.6), thirty-four active > 3.2)) results compared...
<h3>Background and objectives</h3> Detailed information on CD8<sup>+</sup> T cells in rheumatoid arthritis (RA) is still reduced. However, studies animal models of from the authors9 team others suggest a major potential role pathogenesis chronic polyarthritis. In present study authors characterised phenotype cytokine-production profile peripheral blood (PB) synovial fluid (SF) RA patients. <h3>Materials methods</h3> Unstimulated PB SF 40 patients with established were analysed by...
<h3>Background</h3> For the past years there has been a clear increase in interest for T cells autoimmune diseases (<i>1</i>), where it was found that CD8 can have effector or regulatory functions (<i>2,3</i>). Similar findings rheumatoid arthritis, indicate may either pro-inflammatory (<i>4</i>) an anti-inflammatory function mouse models of inflammatory arthritis (<i>5</i>). One argue these results be result two different cell subtypes with enhancing and suppressor down-regulating disease....
<h3>Background</h3> Aberrant accumulation of extracellular matrix (ECM) in multiple organs or fibrosis is one the three hallmarks that characterises pathogenesis systemic sclerosis (SSc), together with immune dysregulation and small vessel vasculopathy. Recent studies have shown CXCL4 (Chemokine CXC motif ligand 4) levels are increased patients SSc correlated skin lung fibrosis.<sup>1</sup> plays key role physiological processes, although it has been also implicated several pathological...