A5114374911- Rheumatoid Arthritis Research and Therapies
- Bone Metabolism and Diseases
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- MicroRNA in disease regulation
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- interferon and immune responses
- Bone health and treatments
- Cell Adhesion Molecules Research
- SARS-CoV-2 and COVID-19 Research
- Mast cells and histamine
- Cancer-related molecular mechanisms research
- Autoimmune and Inflammatory Disorders Research
- Immune cells in cancer
- Osteoarthritis Treatment and Mechanisms
- Bone and Joint Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Circular RNAs in diseases
- Reproductive System and Pregnancy
- Cancer Immunotherapy and Biomarkers
- Toxin Mechanisms and Immunotoxins
Medical University of Vienna
2015-2024
Christian Doppler Laboratory for Thermoelectricity
2018-2023
CeMM Research Center for Molecular Medicine
2015-2016
Austrian Academy of Sciences
2009-2016
Center for Rheumatology
2013-2014
University of Vienna
2003-2013
University of California, Los Angeles
2012
Palmetto Hematology Oncology
2012
Vienna General Hospital
2011
Institute of Immunology
2005-2009
MicroRNAs (miRNA) are a new class of regulatory elements. Altered expression miRNA has been demonstrated in the inflamed joints patients with rheumatoid arthritis (RA). The aim this study was to examine role pathogenesis autoimmune arthritis, using 2 murine models.Collagen-induced (CIA) and K/BxN serum-transfer were induced wild-type (WT) miR-155-deficient (miR-155(-/-) ) mice. severity determined clinically histologically. Anticollagen antibodies cytokines measured by enzyme-linked...
Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a and T-cell-mediated against SARS-CoV-2 immunisation.Patients under RTX treatment (n=74) were vaccinated twice either mRNA-1273 or BNT162b2. Antibodies quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay receptor-binding domain (RBD) of spike protein neutralisation tests. SARS-CoV-2-specific T-cell...
Objective— Activation of peroxisome proliferator-activated receptors (PPARs) by lipid-lowering fibrates and insulin-sensitizing thiazolidinediones inhibits vascular inflammation, atherosclerosis, restenosis. Here we investigate if the vasculoprotective anti-inflammatory enzyme heme oxygenase-1 (HO-1) is regulated PPAR ligands in cells. Methods Results— We show that treatment human endothelial smooth muscle cells with leads to expression HO-1. Analysis HO-1 promoter transient transfection...
Recognition of pathogens by the innate immune system requires proteins that detect conserved molecular patterns. Nucleic acids are recognized cytoplasmic sensors as well endosomal Toll-like receptors (TLRs). It has become evident TLRs require additional to be activated their respective ligands. In this study, we show CD14 (cluster differentiation 14) constitutively interacts with MyD88-dependent TLR7 and TLR9. was necessary for TLR7- TLR9-dependent induction proinflammatory cytokines in...
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, protects against oxidative stress, and shows potent anti-inflammatory effects. Oxidized phospholipids, which are generated during inflammation apoptosis, modulate inflammatory response by inducing expression of several genes including HO-1. Here we investigated signaling pathways transcriptional events involved induction HO-1 gene oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) human...
Abstract The activation of innate immune cells triggers numerous intracellular signaling pathways, which require tight control to mount an adequate response. PI3K pathway is intricately involved in immunity, and its dampens the expression release proinflammatory cytokines myeloid cells. These processes are strictly regulated by antagonist, lipid phosphatase, PTEN, a known tumor suppressor. Importantly, PTEN responsible for elevated production such as IL-6 response TLR agonists, deletion...
Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic are widely accepted frequently used to identify pathological mechanisms validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description appropriate assessment of the distinct histopathological features arthritis: joint inflammation, cartilage damage bone erosion. Therefore, European consortium BeTheCure, consisting 38 academic...
DCs are able to undergo rapid maturation, which subsequently allows them initiate and orchestrate T cell-driven immune responses. DC maturation must be tightly controlled in order avoid random cell activation development of autoimmunity. Here, we determined that 12/15-lipoxygenase-meditated (12/15-LO-mediated) enzymatic lipid oxidation regulates fine-tunes consecutive Specifically, 12/15-LO activity the threshold via generation phospholipid products induced an antioxidative response...
Maturation of dendritic cells (DCs) induced by pathogen-derived signals via TLRs is a crucial step in the initiation an adaptive immune response and therefore has to be well controlled. In this study, we demonstrate that oxidized phospholipids (ox-PLs), which are generated during infections, apoptosis, tissue damage, interfere with DC activation, preventing their maturation. ox-PLs blocked TLR-3- TLR-4-mediated induction costimulatory molecules CD40, CD80, CD83, CD86, cytokines IL-12 TNF, as...
Lipid metabolism and receptor-mediated signaling are highly intertwined processes that cooperate to fulfill cellular functions safeguard homeostasis. Activation of Toll-like receptors (TLRs) leads a complex response, orchestrating diverse range inflammatory events need be tightly controlled. Here, we identified the GPI-anchored Sphingomyelin Phosphodiesterase, Acid-Like 3B (SMPDL3B) in mass spectrometry screening campaign for membrane proteins co-purifying with TLRs. Deficiency Smpdl3b...
Objectives Bone destruction in rheumatoid arthritis is mediated by osteoclasts (OC), which are derived from precursor cells of the myeloid lineage. The role two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2) non-classical (which CD115 positive, but low CCR2), serving as precursors for OC still elusive. Methods We investigated CCR2 −/− mice, lack circulating monocytes, crossed into hTNFtg mice extent joint damage. analysed subsets K/BxN serum transfer flow cytometry....
Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are the most commonly used diagnostic markers of arthritis (RA). These predominantly IgM or IgG isotype. Other subtypes both – particularly IgA isotypes- other autoantibodies such as RA33 have been repeatedly reported but their value has still not fully elucidated. Here, we investigated prevalence IgA, RF, ACPA in patients with RA. To determine specificity sensitivity sera from 290 RA (165 early 125 established disease),...
Abstract Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis model formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome multiple murine arthritis models its removal...
Oxidized phospholipids (OxPLs) that are abundant in atherosclerotic lesions increasingly recognized as context-dependent lipid mediators demonstrating both pro- and antiinflammatory activities. Molecular mechanisms of their effects largely unknown. Here we present novel information on the whereby OxPLs modulate activation TLR4 by lipopolysaccharide (LPS).We show, using several cell types various inflammatory genes readouts, different classes molecular species do not stimulate but exert...
Abstract Objective To investigate the mechanisms leading to influx of inflammatory hematopoietic cells into synovial membrane and role tumor necrosis factor receptor I (TNFRI) TNFRII in this process an animal model rheumatoid arthritis (RA). Methods We performed bone marrow transplantations human TNF–transgenic mice using from wild‐type, TNFRI −/− , TNFRI/II as donors assessed severity histologically. Generation osteoclasts different genotypes was analyzed vitro vivo. Apoptosis annexin V...
Objective Arthritis is frequently seen in human lupus, but rarely lupus models. Pristane-induced (PIL) can be induced various mouse strains such as BALB/c and C57BL/6. We herein characterize clinical histological features of arthritis the context systemic provide a prudent comparison with models rheumatoid (RA). Methods A total 57 mice received pristane (PIL group) were analyzed for serum autoantibodies (anti-chromatin-, -histone, -Sm, -dsDNA), well histopathology joints, lungs kidneys....
Abstract Objective The binding of abatacept (CTLA‐4Ig) to the B7 ligands CD80 and CD86 prevents engagement CD28 on T cells thereby effector cell activation. In addition, a direct effect CTLA‐4Ig antigen‐presenting (APCs) could contribute therapeutic effect. To further elucidate mechanism CTLA‐4Ig, we performed phenotype functional analyses APCs in patients with rheumatoid arthritis (RA) before after initiation therapy. Methods Peripheral blood mononuclear were analyzed at 2 4 weeks...
Objective. Abatacept (CTLA-4Ig) blocks CD28-mediated T cell activation by binding to the costimulatory B7 ligands CD80/CD86 on antigen presenting cells. Costimulatory molecules, however, can also be expressed cells upon activation. Therefore, aim of our study was investigate direct effects CTLA-4Ig distinct subsets in RA patients. Methods. Phenotypic and functional analyses CD4+ cells, including FoxP3+ CD25+ regulatory (Treg), from patients were performed before during therapy. In addition...