A5043180587- Systemic Lupus Erythematosus Research
- Autoimmune and Inflammatory Disorders Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Dermatology and Skin Diseases
- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- IL-33, ST2, and ILC Pathways
- Liver Disease Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Liver Diseases and Immunity
- Asthma and respiratory diseases
- Single-cell and spatial transcriptomics
- Lymphoma Diagnosis and Treatment
- Extracellular vesicles in disease
- DNA Repair Mechanisms
- Down syndrome and intellectual disability research
- Immune cells in cancer
- NF-κB Signaling Pathways
- Allergic Rhinitis and Sensitization
- Chemokine receptors and signaling
- Parasites and Host Interactions
Dublin City University
2023-2024
University of Ioannina
2024
Trinity College Dublin
2015-2023
St. Vincent's University Hospital
2021-2023
Newcastle University
2013-2022
University College Dublin
2021-2022
University of Gothenburg
2021
Sahlgrenska University Hospital
2021
Pirogov Russian National Research Medical University
2021
City Clinical Hospital
2021
Specific B-cell subsets can regulate T-cell immune responses, and are termed regulatory B cells (Breg). The majority of Breg described in mouse man have been identified by IL-10 production known to suppress allergy autoimmunity. However, cell mediated suppression, independent IL-10, also occurs. Here we show that play a critical role regulating humoral immunity CD4+CXCR5+PD-1+ follicular helper T cells, inflammation autoimmune disease through elevated expression PD-L1. We these resistant...
Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development a phenomenon known as the atopic march. Although genetic and environmental factors are contribute AD asthma, mechanisms underlying march remain poorly understood. Filaggrin loss-of-function mutations major predisposer for of progression AD-associated asthma.We sought experimentally address whether filaggrin mice lead spontaneous eczematous inflammation aberrant...
Group 2 innate lymphoid cells (ILC2s) are important effector driving the initiation of type immune responses leading to adaptive T helper (Th2) immunity. Here we show that ILC2s dynamically express checkpoint inhibitor molecule PD-L1 during pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between and CD4+ did not inhibit cell response, but PD-L1-expressing stimulated increased expression GATA3 production IL-13 by Th2 both in vitro vivo. Conditional deletion on impaired early...
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...
Atopic dermatitis (AD) is one of the most common skin diseases with a multifactorial etiology. Mutations leading to loss barrier function are associated development AD group 2 innate lymphoid cells (ILC2) promoting acute inflammation. Filaggrin-mutant (Flg
Low Density Granulocytes (LDGs), which appear in the peripheral blood mononuclear cell layer of density-separated blood, are seen cancer, sepsis, autoimmunity and pregnancy. Their significance ANCA vasculitis (AAV) is little understood. As these cells bear autoantigens associated with this condition have been found to undergo spontaneous NETosis other diseases, we hypothesised that they were key drivers vascular inflammation. We LDGs comprise a 3-fold higher fraction total granulocytes...
Background MicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease arthralgia “at-risk individuals”. Methods Serum was collected from HC subjects (N = 20), 50), 10), addition to subgroup the post-methotrexate (MTX) 18). The FirePlex Immunology-V2 panel selected...
While autoantibodies are used in the diagnosis of rheumatoid arthritis (RA), function B cells inflamed joint remains elusive. Extensive flow cytometric characterization and SPICE algorithm analyses single-cell synovial tissue from patients with RA revealed accumulation switched double-negative memory programmed death-1 receptor-expressing (PD-1-expressing) at site inflammation. Accumulation was mediated by CXCR3, evident observed increase CXCR3-expressing compared periphery, differential...
Abstract Atopic dermatitis (AD) is a common inflammatory skin disease affecting up to 20% of children and 3% adults worldwide associated with dysregulation the barrier. Although type 2 responses are implicated in AD, emerging evidence indicates potential role for IL-17A signaling axis AD pathogenesis. In this study we show that filaggrin mutant mouse model spontaneous IL-17RA deficiency (Il17ra−/−) resulted severe exacerbation inflammation. Interestingly, Il17ra−/− mice without mutation also...
Infection with parasite helminths induces potent modulation of the immune system host. Epidemiological and animal studies have shown that helminth infections can suppress or exacerbate unrelated autoimmune, allergic, other inflammatory disorders. There is growing evidence infection-mediated suppression bystander responses influenced by alterations in intestinal microbiome modulating metabolic functions infected We analyzed fecal microbiota mice adult male Schistosoma mansoni worms, which are...
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...
Currently available therapies for rheumatoid arthritis (RA) are inadequate to alleviate the inflammation and reduce joint damage. While immune-regulatory effect of human mesenchymal/stromal stem cells (MSCs) extracellular vesicles (EVs) has been tested in many inflammation-related diseases, little is known regarding their on patients with RA. Thus, we assessed MSCs MSC-EVs (from naïve or IFN-β-primed MSCs) CD4+ T from Moreover, investigated RA patients-derived synovial fibroblasts (FLS)....
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...
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...
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...
The helminth Schistosoma mansoni modulates the infected host's immune system to facilitate its own survival, by producing excretory/secretory molecules that interact with a variety of cell types including those system. Herein, we characterise S. adult male worm secretome and identify 111 proteins, 7 vaccine candidates several potential immunomodulatory activity. Amongst present in secretome, 17-19kDa protein analogous human cyclophilin A was identified. Given ability modulate regulating...
Atopic dermatitis (AD) is associated with a dysregulation of the skin barrier and may predispose to development secondary allergic conditions, such as asthma. Tmem79ma/ma mice harbor mutation in gene encoding Transmembrane Protein 79 (or Mattrin), which has previously been AD. As result Tmem79 mutation, these have defective develop spontaneous inflammation. In this study, were assessed for underlying immunological response lung inflammation.Development inflammation was analyzed. We further...
Immune checkpoint inhibitors have revolutionised cancer treatment; however, immune-related adverse events do occur, with up to 7% developing inflammatory arthritis. Common rheumatoid arthritis therapies such as methotrexate, prednisolone and biologics been used treat this in small, uncontrolled case series varying success. In of personalised medicine, we report the first use tofacitinib, a small molecular inhibitor Janus kinase-signal transducer activator transcription pathway,...
The majority of studies examining antigen-presenting cell (APC) function have focused on the capture and presentation antigens released from pathogens or damaged cells. However, antigen-specific B cells are also capable efficiently extracting that either tethered to, integrally part plasma membrane various target In this study we show highly efficient at integral components extracellular matrix (ECM) for subsequent presentation. particular demonstrate specific aggrecan, an component...
Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality life and resulting in social isolation. Fatigue highlighted by as priority for research patient support groups were involved designing this trial. the first randomised controlled trial to investigate treatment fatigue PBC. The protocol innovative it utilises novel magnetic resonance spectroscopy...
Objective Juvenile idiopathic arthritis ( JIA ) is the most common inflammatory in children; however, an aggressive, erosive of little‐known immunologic mechanism occurs 20 times more frequently children with Down syndrome. This study was undertaken to characterize T cell and B polyreactivity, follicular helper (Tfh) cell, peripheral (Tph) Treg responses, synovial inflammation syndrome–associated DA ). Methods Multiparametric flow cytometric analysis Simplified Presentation Incredibly...