A5013967314- Immune Response and Inflammation
- Rheumatoid Arthritis Research and Therapies
- Gut microbiota and health
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Mycobacterium research and diagnosis
- Psoriasis: Treatment and Pathogenesis
- NF-κB Signaling Pathways
- Inflammasome and immune disorders
- Inflammatory mediators and NSAID effects
- Cytokine Signaling Pathways and Interactions
- Inflammatory Bowel Disease
- Helicobacter pylori-related gastroenterology studies
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Pediatric health and respiratory diseases
- Bone Metabolism and Diseases
- Orthopedic Infections and Treatments
- Dermatology and Skin Diseases
- Osteoarthritis Treatment and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Oral microbiology and periodontitis research
- Bartonella species infections research
New York University
2016-2020
Radboud University Nijmegen
2010-2019
Radboud University Medical Center
2010-2019
University Medical Center
2016-2018
Radboud Institute for Molecular Life Sciences
2017
University of Córdoba
2017
Instituto Maimónides de Investigación Biomédica de Córdoba
2017
Hospital Universitario Fundación Jiménez Díaz
2017
Universidad Autónoma de Madrid
2017
Hospital Universitario Reina Sofía
2017
TLRs may contribute to the progression of rheumatoid arthritis through recognition microbial or host-derived ligands found in arthritic joints. Here, we show that TLR2 and TLR4, but not TLR9, are involved pathogenesis autoimmune play distinct roles regulation T cells cytokines. We investigated involvement TLR2, TLR9 using IL-1 receptor antagonist–knockout (IL1rn–/–) mice, which spontaneously develop an cell–mediated arthritis. Spontaneous onset was dependent on TLR activation by flora, as...
Degeneration of extracellular matrix cartilage leads to the production molecules capable activating immune system via Toll-like receptor 4 (TLR-4). The objective this study was investigate involvement TLR-4 activation in development and progression autoimmune destructive arthritis.A naturally occurring antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, first characterized using mouse macrophages human dendritic cells (DCs). Mice with collagen-induced arthritis...
Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients individuals at-risk for disease development. This suggests the possibility that could be a site of autoimmunity generation RA, perhaps response to microbiota changes. We therefore sought test whether RA microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity. 16S rRNA gene high-throughput sequencing was utilized compare bacterial community...
Abstract Objective To evaluate the expression of Toll‐like receptors (TLRs) 3 and 7 in synovium to study potential differences maturation cytokine production mediated by TLR‐2, TLR‐3, TLR‐4, TLR‐7/8 dendritic cells (DCs) from rheumatoid arthritis (RA) patients DCs healthy controls. Methods Synovial TLR‐3 TLR‐7 RA was studied using immunohistochemistry. Monocyte‐derived controls were cultured for 6 days subsequently stimulated 48 hours via TLR‐mediated pathways (lipoteichoic acid, Pam Cys,...
Abstract Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well of endogenous ligands, which released during inflammation and cell stress. The exogenous ligands depends on TLRs, abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR found to present RA serum fluid significantly increased, compared with healthy volunteers patients systemic sclerosis lupus erythematosus. Identification novel might contribute...
Abstract Objective S100A8 and S100A9 are two Ca 2+ binding proteins classified as damage‐associated molecular patterns or alarmins that found in high amounts the synovial fluid of osteoarthritis (OA) patients. The purpose this study was to investigate whether and/or can interact with chondrocytes from OA patients increase catabolic mediators. Methods Using immunohistochemistry, we stained for protein, matrix metalloproteinases (MMPs), a cartilage‐breakdown epitope specific MMPs (VDIPEN)...
Increasing epidemiologic evidence supports a link between periodontitis and rheumatoid arthritis. The actual involvement of in the pathogenesis arthritis underlying mechanisms remain, however, poorly understood. We investigated influence concomitant on clinical histopathologic characteristics T cell-mediated experimental evaluated modulation type II collagen (CII)-reactive Th cell phenotype as potential mechanism. Repeated oral inoculations periodontal pathogens Porphyromonas gingivalis...
The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for property GAG remain to be elucidated. In present study we used vitro PBMC stimulation assays demonstrate, inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), blocks IL-1 signalling. cannot suppress presence neutralizing antibodies against...
Generation of different CD4 T cell responses to commensal and pathogenic bacteria is crucial for maintaining a healthy gut environment, but the associated cellular mechanisms are poorly understood. Dendritic cells (DCs) macrophages (Mfs) integrate microbial signals direct adaptive immunity. Although role DCs in initiating well appreciated, how Mfs contribute generation intestinal microbes unclear. Th17 critical mucosal immune protection at steady state induced by bacteria, such as segmented...
Perturbations of the intestinal microbiome have been observed in patients with new-onset and chronic autoimmune inflammatory arthritis. However, it is currently unknown whether these alterations precede development arthritis or are rather a consequence disease. Modulation microbiota by oral antibiotics germ-free condition can prevent mice. Yet, therapeutic potential modulation after onset not well characterized. We here show that microbial community undergoes marked changes preclinical phase...
Interleukin-1 receptor antagonist-deficient (IL-1Ra-/-) mice spontaneously develop an inflammatory and destructive arthritis due to unopposed excess IL-1 signaling. In this study, the role of Th17 cells effect neutralization IL-17, IL-1, tumor necrosis factor alpha (TNFalpha) were investigated in IL-1-driven murine model.T isolated from IL-1Ra-/- wild-type (WT) stained for IL-17 interferon-gamma, with results assessed by fluorescence-activated cell sorting analysis. To investigate...
Background: Rheumatoid arthritis (RA) has been associated with an increased risk of infections, but the underlying pathways have not yet identified. Toll-like receptors (TLR) probably play a role in synovial inflammation and may also contribute to understanding infections RA. Objectives: To investigate if expression TLR3 TLR7 RA correlates that inflammatory cytokines, assess whether this functional consequences for local cytokine production study potential links between TLR3/7 axis TLR4...
Abstract Objective Toll‐like receptors (TLRs) may activate innate and adaptive immune responses in rheumatoid arthritis (RA) through recognition of microbial as well endogenous ligands that have repeatedly been found arthritic joints. The objective this study was to investigate the involvement TLR‐2 TLR‐4 development chronic destructive streptococcal cell wall (SCW)–induced arthritis, which interleukin‐1 (IL‐1)/IL‐17–dependent T cell–driven pathologic changes replace macrophage‐driven acute...
Rheumatoid arthritis, which is associated with elevated levels of S100A8 and S100A9, characterized by severe bone erosions caused enhanced osteoclast formation activity. The aim the present study was to investigate role S100A9 in osteoclastic destruction murine antigen-induced arthritis (AIA).Bone analyzed arthritic knee joints S100A9-deficient mice protein expression also lacking, wild-type (WT) controls. Osteoclast precursors from WT were differentiated into osteoclasts vitro....
Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn -/- mice) spontaneously develop arthritis and are susceptible to other diseases such as psoriasis, diabetes, encephalomyelitis; however, the mechanisms increased susceptibility these phenotypes poorly understood. We investigated role (IL-1Ra) regulation microbiota, assessed involvement subsets innate adaptive mucosal immune responses...
Abstract Objective The pathogenesis of rheumatoid arthritis is often linked to bacterial infections. present study was undertaken develop a mouse model chronic destructive induced by repeated intraarticular (IA) exposure cell wall fragments and investigate the cytokine dependence this model. Methods Mice that were deficient in various cytokines injected IA with Streptococcus pyogenes on days 0, 7, 14, 21. development compared between groups mice lacking different cytokines, assess which...
ABSTRACT Bartonella quintana is a gram-negative microorganism that causes trench fever and chronic bacteremia. B. lipopolysaccharide (LPS) was unable to induce the production of proinflammatory cytokines in human monocytes. Interestingly, LPS potent antagonist Toll-like receptor 4 (TLR4), as it inhibited both mRNA transcription release tumor necrosis factor alpha, interleukin 1β (IL-1β), IL-6 by Escherichia coli monocytes, at ratios ranging from 1,000:1 10:1 ( E. LPS). Likewise, blocked...
Abstract Objective To investigate whether S100A8 is actively involved in matrix metalloproteinase (MMP)–mediated chondrocyte activation. Methods and S100A9 proteins were detected inflamed knee joints from mice with various forms of murine arthritis, using immunolocalization. Murine cell line H4 was stimulated proinflammatory cytokines or recombinant S100A8. Messenger RNA (mRNA) protein levels measured reverse transcriptase–polymerase chain reaction intracellular fluorescence‐activated...
Hyperactivation of innate immunity by Toll-like receptors (TLRs) can contribute to the development autoinflammatory or autoimmune diseases. This study evaluated activation Tyro3, Axl, Mer (TAM) receptors, physiologic negative regulators TLRs, their agonists, growth arrest-specific protein 6 (GAS-6) and S, in prevention collagen-induced arthritis (CIA).Adenoviruses overexpressing GAS-6 S were injected intravenously intraarticularly into mice during CIA. Splenic T helper cell subsets from...
Intestinal microbiota are associated with the development of inflammatory arthritis. The aim this study was to dissect intestinal mucosal immune responses in preclinical phase arthritis and determine whether presence Th17 cells, beyond involvement cytokine interleukin-17 (IL-17), is required for development, cells depends on composition host microbiota.Mucosal T cell production IL-17, interferon-γ, tumor necrosis factor α (TNFα), IL-22, granulocyte-macrophage colony-stimulating (GM-CSF)...
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory autoimmune conditions, but no definitive role pathogenesis has been established. Here, we show that skin-targeted overexpression causes generalized, severe psoriasiform dermatitis with spontaneous development debilitating psoriatic arthritis-like joint disease. The skin...