A5049215002- Salivary Gland Disorders and Functions
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Systemic Sclerosis and Related Diseases
- Chemokine receptors and signaling
- Angiogenesis and VEGF in Cancer
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Rheumatoid Arthritis Research and Therapies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Coronary Interventions and Diagnostics
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- Immune responses and vaccinations
- Psoriasis: Treatment and Pathogenesis
- Adolescent and Pediatric Healthcare
- Cerebrovascular and Carotid Artery Diseases
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Lymphatic System and Diseases
- Diabetes and associated disorders
- Protein Tyrosine Phosphatases
- IL-33, ST2, and ILC Pathways
Princess Máxima Center
2024
University Medical Center Utrecht
2016-2023
Utrecht University
2018-2022
San Antonio College
2017
Instituto de Medicina Molecular João Lobo Antunes
2014-2015
Instituto Português de Oncologia de Coimbra Francisco Gentil
2015
Guangzhou Blood Center
2013-2014
Instituto Portugues do Sangue e da Transplantacao, IP
2013-2014
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...
The interferon (IFN) signature is related to disease activity and vascular in systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS) represents a promising therapeutic target. Quantification of the IFN currently performed by gene expression analysis, limiting its current applicability clinical practice. Therefore, objective this study was establish an easy measure biomarker for signature.Serum levels galectin-9, CXCL-10 (IP-10) tumour necrosis factor receptor type II (TNF-RII)...
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...
Diabetic patients have a significantly worse prognosis after an acute myocardial infarction (AMI) than their counterparts. Previous studies shown that the number of circulating endothelial progenitor cells (EPCs) increase early AMI in normoglycemic patients. However, it is well known type 2 diabetes mellitus (DM) associated with impaired function and reduced EPCs levels. Nonetheless, few analyzed response diabetics to EPC pre-diabetic has not been reported yet. Therefore, we hypothesized...
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...
Cytosolic DNA-sensing pathway stimulation prompts type I IFN (IFN-I) production, but its role in systemic IFN-I activation primary SS (pSS) is poorly studied. Here we investigate the responsiveness of pSS monocytes and plasmacytoid dendritic cells (pDCs) to stimulator interferon genes (STING) relation compare this with SLE.Expression receptors cGAS, IFI16, ZBP-1 DDX41, signalling molecules STING, TBK1 IRF3, positive negative STING regulators, IFN-I-stimulated MxA, IFI44, IFI44L, IFIT1 IFIT3...
To investigate miRNA expression in relation to transcriptomic changes plasmacytoid dendritic cells (pDCs) SLE and APS. pDCs are major producers of IFNα APS, miRNAs emerging as regulators pDC activation.miRNA mRNA were measured by OpenArray RNA-sequencing SLE, + APS (APS secondary SLE) primary (PAPS) patients. The profile patients was compared with the pattern TLR7-activated pDCs.Among 131 detected pDCs, 35, 17 21 had a significantly lower level PAPS patients, respectively, healthy controls...
The objective of this study was to test the capacity a newly developed fusion protein interleukin 4 (IL-4) and IL-10 [IL4-10 (FP)] shift multiple pro-inflammatory pathways towards immune regulation, inhibit activity in arthritis models. effects IL4-10 FP comparison with IL-4, IL-4 plus on pro- anti-inflammatory mediators, T cells immunoglobulin (Ig) receptors favour immunoregulatory were studied. In addition, ex-vivo in-vivo models investigated. robustly inhibited cytokine [IL-1β, tumour...
Semaphorin (Sema)4A is a transmembrane glycoprotein that elevated in several autoimmune diseases such as systemic sclerosis, rheumatoid arthritis and multiple sclerosis. Sema4A has key role the regulation of Thelper Th1 Th2 differentiation we recently demonstrated CD4+ T cell activation induces expression Sema4A. However, autocrine on Th remains unknown. Naïve cells from healthy controls were sorted differentiated into Th1, Th17 presence or absence neutralizing antibody against receptor...
To examine the role of Tie2 signalling in macrophage activation within context inflammatory synovial microenvironment present patients with RA and PsA.
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of the exocrine glands and prominent B cell hyperactivity. Considering key role monocytes in promoting hyperactivity, we performed RNA-sequencing analysis CD14 + from patients with pSS, non-Sjögren’s sicca (nSS), healthy controls (HC). We demonstrated that transcriptomic profile pSS enriched intermediate non-classical monocyte profiles, confirmed increased frequency flow-cytometry analysis....
Trained immunity - or innate immune memory can be described as the long-term reprogramming of cells towards a hyperresponsive state which involves intracellular metabolic changes. has been linked to atherosclerosis. A subgroup patients with primary Sjögren's syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating hyperactivation. Here, we studied link between IFNs and trained in an
Background Considering the important role of miRNAs in regulation post–transcriptional expression target genes, we investigated circulating small non-coding RNAs (snc)RNA levels patients with primary Sjögren's syndrome (pSS). In addition assessed if serum sncRNA can be used to differentiate specific disease features. Methods Serum RNA was isolated from 37 pSS as well 21 incomplete Syndrome (iSS) and 17 healthy controls (HC) allocated two independent cohorts: discovery validation. OpenArray...
Objective Type 2 conventional dendritic cells (cDC2s) are key orchestrators of inflammatory responses, linking innate and adaptative immunity. Here we explored the regulation immunological pathways in cDC2s from patients with primary Sjögren’s syndrome (pSS). Methods RNA sequencing circulating pSS, non-Sjögren’s sicca healthy controls (HCs) was exploited to establish transcriptional signatures. Phenotypical functional validation performed independent cohorts. Results Transcriptome pSS...
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...
Chronic urticaria is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, Th17 and Tc17 have been implicated in autoimmune diseases; however, their role not clear yet.For the study we recruited 20 patients [10 of them had autoreactive chronic spontaneous (positive autologous intradermal serum test response, ASST+), other 10 were nonautoreactive (ASST-)] 17 healthy age- gender-matched controls (HG). The frequency functional activity Th17/Tc17 Th1/Tc1 cells...
What is already known on this subject ► TRIM21/Ro52 a major autoantibody target in pSS and regulates downstream signalling of type I IFNs.► Apoptosis-associated surface expression TRIM21 non-immune cells associated with enhanced binding anti-Ro52 autoantibodies. study adds► Enhanced IFNproducing immune from patients an IFN signature B cell hyperactivity.► expressed the nonapoptotic antigen-presenting its by IFN-β exposure. How might impact clinical practice► Elucidating relationship between...
Objectives: Considering the critical role of microRNAs (miRNAs) in regulation cell activation, we investigated their circulating type-2 conventional dendritic cells (cDC2s) patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from peripheral blood. A discovery cohort (15 pSS, 6 HC) was used screen expression 758 miRNAs and a replication 11 confirm differential 18 identified targets. Novel targets for two replicated by...
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....
Introduction CCR9+ Tfh-like pathogenic T helper (Th) cells are elevated in patients with primary Sjögren’s syndrome (pSS) and indicated to play a role pSS immunopathology. Here we delineate the Th cell-specific transcriptome study molecular dysregulation of these patients. Methods CCR9+, CXCR5+ CCR9-CXCR5- from blood 7 healthy controls (HC) were FACS sorted RNA sequencing was performed. Computational analysis used identify differentially expressed genes (DEGs), coherent gene expression...
Human leukocyte antigen (HLA) restriction of conventional T-cell targeting introduces complexity in generating therapy strategies for patients with cancer diverse HLA-backgrounds. A subpopulation atypical, major histocompatibility complex-I related protein 1 (MR1)-restricted T-cells, distinctive from mucosal-associated invariant T-cells (MAITs), was recently identified recognizing currently unidentified MR1-presented cancer-specific metabolites. It is hypothesized that the MC.7.G5 MR1T-clone...
Abnormalities in monocytes and peripheral blood dendritic cells (DC) subsets have been reported systemic lupus erythematosus (SLE). We aim to clarify the tolerogenic or inflammatory role of these based on ICOSL IFN- α chemokine mRNA expression, respectively, after cell purification. The study included 18 SLE patients with active disease (ASLE), 25 inactive (ISLE), 30 healthy controls (HG). In purified plasmacytoid DC (pDC) was observed a lower expression ASLE an increase ISLE; similarly,...