A5007663454- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Cell Adhesion Molecules Research
- Autoimmune and Inflammatory Disorders Research
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Spondyloarthritis Studies and Treatments
- Lymphoma Diagnosis and Treatment
- Chemokine receptors and signaling
- Osteoarthritis Treatment and Mechanisms
- Web and Library Services
- Immunodeficiency and Autoimmune Disorders
- Pregnancy and Medication Impact
- Ocular Diseases and Behçet’s Syndrome
- Social Media in Health Education
- NF-κB Signaling Pathways
- Psoriasis: Treatment and Pathogenesis
- interferon and immune responses
- MicroRNA in disease regulation
- Phosphodiesterase function and regulation
Trinity College Dublin
2016-2025
St. Vincent's University Hospital
2015-2024
University College Dublin
2015-2024
European League Against Rheumatism
2023
University of Gothenburg
2021
Sahlgrenska University Hospital
2021
Pirogov Russian National Research Medical University
2021
City Clinical Hospital
2021
Shanxi Medical University
2021
Second Hospital of Shanxi Medical University
2021
This study examines the relationship between synovial hypoxia and cellular bioenergetics with inflammation.Primary rheumatoid arthritis fibroblasts (RASF) were cultured hypoxia, dimethyloxalylglycine (DMOG) or metabolic intermediates. Mitochondrial respiration, mitochondrial DNA mutations, cell invasion, cytokines, glucose lactate quantified using specific functional assays. RASF metabolism was assessed by XF24-Flux Analyzer. structural morphology transmission electron microscopy (TEM). In...
Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, sodium glucose co-transporter (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the of SGLT2 inhibitors human have not been extensively explored. Here, we show that canagliflozin-treated cells are compromised their ability activate,...
Th17 cells are an important therapeutic target in autoimmunity. However, it is known that exhibit considerable plasticity, particularly at sites of autoimmune inflammation. can switch to become ex-Th17 no longer produce IL-17 but IFN-γ. These also called nonclassical Th1 because their ability IFN-γ, similar cells; however, unclear whether they resemble or terms function and regulation, have a pathogenic role We compared the phenotypic functional features human Th17, Th1, cell populations....
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy multiple cancer types, concomitant immune-related adverse events, including arthralgia inflammatory arthritis (IA) some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along transcriptomics of synovial tissue from stages rheumatoid...
Abstract The inflammatory CD40–CD40L pathway is implicated in various autoimmune diseases, but the activity status of this stages rheumatoid arthritis (RA) progression unknown. In study, we used gene signatures CD40L stimulation derived from human immature dendritic cells and naive B to assess expression CD40-downstream genes synovial tissues anti-citrullinated protein Ab–positive arthralgia, undifferentiated (UA), early RA, established RA cohorts comparison with healthy donors....
Objectives Immune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) psoriatic (PsA), however, nature these interactions synovial pathology two pathotypes can differ. Identifying immune-stromal crosstalk at site inflammation RA PsA challenging. This study creates first global transcriptomic analysis inflamed joint investigates inflammation. Methods Single profiling 178 000 tissue cells from five patients with four RA, importantly, without prior sorting...
In autoimmune diseases such as rheumatoid arthritis (RA), regulatory T cells (Tregs) fail to constrain inflammation; however, the reasons for this are unclear. We investigated cell regulation in RA joint. Tregs from synovial fluid suppressed autologous responder cells; when compared with healthy control peripheral blood, they were significantly less suppressive. Despite their reduced suppressive activity, joint highly proliferative and expressed FOXP3, CD39, CTLA-4, which markers of...
Abstract During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in manner similar that observed tumour cells. While TLRs been implicated pathogenesis of rheumatoid arthritis (RA), their role regulating cellular metabolism synovial cells, however, is still unknown. In this study, we investigated effect TLR2-activation on mitochondrial function and bioenergetics primary RA-synovial fibroblast (RASFC),...
Objective This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease implications for therapy. Methods PsA was enzymatically/mechanically digested to generate single cell suspensions. Frequencies of CD4, CD8, T-helper 1 (Th1), Th17 exTh17 cells, using CD161 as a marker plasticity, were determined by flow cytometry matched peripheral blood. Synovial T-cell polyfunctionality assessed relation Disease Activity PSoriatic...
Dendritic cells (DC) have a key role in the initiation and progression of inflammatory arthritis (IA). In this study, we identified DC population that derive from monocytes, characterized as CD209/CD14 + DC, expressing classical markers (HLADR, CD11c) Mo-DC marker (CD209), while also retaining monocytic CD14. This is present circulation Healthy Control (HC), with increased frequency Rheumatoid Arthritis (RA) Psoriatic arthritic (PsA) patients. We demonstrate, for first time, circulatory IA...
Objectives To explore perceptions, barriers and patterns of social media (SM) use among rheumatology fellows basic scientists. Methods An online survey was disseminated via Twitter, Facebook by email to members the Emerging European League Against Rheumatism Network. Questions focused on general demographics, frequency types SM use, reasons use. Results Of 233 respondents (47 countries), 72% were aged 30–39 years, 66% female. 83% active users at least one platform 71% using professionally....
BackgroundAlthough neoangiogenesis is a hallmark of chronic inflammatory diseases such as arthritis and many cancers, therapeutic agents targeting the vasculature remain elusive. Here we identified miR-125a an important regulator angiogenesis.MethodsMiRNA levels were quantified in Psoriatic Arthritis (PsA) synovial-tissue by RT-PCR compared to macroscopic synovial vascularity. HMVEC transfected with anti-miR-125a angiogenic mechanisms using tube formation assays, transwell invasion chambers,...
Monocyte-derived Dendritic cells (Mo-DC) are a distinct DC subset, involved in inflammation and infection, they originate from monocytes upon stimulation the circulation their activation function may vary autoimmune diseases. In this study we investigate differences Mo-DC differentiation patients with Rheumatoid (RA) compared to Psoriatic arthritis (PsA). A significant increase marker CD209, paralleled by corresponding decrease monocytic CD14, was demonstrated RA PsA, as early one day post...
Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neovascularization, immune cell infiltration, and synovial hyperplasia, which leads to degradation of articular cartilage bone, subsequent functional disability. Dysregulated angiogenesis, hypoxia, infiltration result in ‘bioenergetic crisis’ the inflamed joint further exacerbates invasiveness. Several studies have examined this vicious cycle between metabolism, immunity, inflammation role metabolites play...
Objectives This study investigates pathogenic and protective polyfunctional T-cell responses in patient with rheumatoid arthritis (RA), individuals at risk (IAR) healthy control (HC) synovial-tissue biopsies identifies the presence of a novel population T-cells that are enriched RA joint prior to development clinical inflammation. Methods Pathway enrichment analysis previously obtained RNAseq data synovial from (n=118), IAR (n=20) HC (n=44) was performed. Single-cell tissue suspensions...
Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for diagnosis RA, however 20–30% patients ACPA negative. status delineator RA endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells CD4 cell proinflammatory...
Abstract Introduction Obesity is a worldwide epidemic, with over 1 billion people living obesity. It associated an increased risk of 200 chronic co-morbidities, including susceptibility to infection. Numerous studies have highlighted the dysfunction caused by obesity on wide range immune cell subsets, dendritic cells (DCs). DCs are innate sentinels that bridge and adaptive systems. provide critical signals instruct shape response. Our group has previously reported from display defective...
CD141+ DC are implicated in antiviral and antitumor immunity. However, mechanistic studies autoimmune disease limited. This is the first study to our knowledge examining disease, specifically inflammatory arthritis (IA). We identified significant enrichment of inflamed synovial joint, which were transcriptionally distinct from IA healthy control (HC) blood significantly more activated, they exhibited increased responsiveness TLR3. Synovial represent a bone fide population that CD1c+ DC....
To investigate the functional role of miR-23a in synovial fibroblasts (SFC) activation psoriatic arthritis (PsA).Differential expression miR-23a-27a-24-2 cluster was identified by real-time quantitative PCR PsA tissue and peripheral blood mononuclear cells (PBMC) compared to osteoarthritis (OA) correlated with disease activity. For regulation experiments, were cultured Toll-like receptor (TLR) ligands pro-inflammatory cytokines. SFC transfected a inhibitor assess effect on migration,...
Rheumatoid arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It well appreciated that the pathogenic hallmark RA mass influx inflammatory cells into joint. However, role dendritic (DC) may play in this milieu still relatively unexplored. Moreover, contribution unique synovial microenvironment has on DC maturation unknown. Using monocyte-derived (MoDC), we established an in-vitro model to recapitulate explore maturation. MoDC treated with...
Objective To examine the role of synovial CD1c + DCs in patients with Inflammatory Arthritis (IA) a specific focus on transcriptional and maturation signatures that govern their function. Methods RNA sequencing was performed healthy control (HC) peripheral blood (PB), IA PB, fluid (SF) DCs. Multiparametric flow-cytometry SPICE analysis were used to site [SF Synovial Tissue (ST) CD1c+DCs] disease characteristics DCs, while functional assays such as antigen processing, activation, MMP...