A5052191975- MicroRNA in disease regulation
- Rheumatoid Arthritis Research and Therapies
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Eosinophilic Esophagitis
- Systemic Lupus Erythematosus Research
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Osteoarthritis Treatment and Mechanisms
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Signaling Pathways in Disease
- Autoimmune and Inflammatory Disorders Research
- Tendon Structure and Treatment
- Spondyloarthritis Studies and Treatments
- Bone and Joint Diseases
- Musculoskeletal synovial abnormalities and treatments
- CAR-T cell therapy research
University of Glasgow
2016-2025
Versus Arthritis
2018-2025
Centre for Immunity, Infection and Evolution
2018-2023
NHS Greater Glasgow and Clyde
2022
Institute of Infection and Immunity
2013-2021
Universities Scotland
2017
Glasgow Life
2013
University of Naples Federico II
2012
Abstract Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient ST2, receptor for the latest member of IL-1 family, IL-33, have impaired immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved differentiation and activation AAM during airway inflammation. report here IL-33 changed quiescent phenotype alveolar toward an expressed mannose receptor, IL-4Rα, produced high levels CCL24 CCL17 IL-13-dependent manner IL-33-induced...
MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role inflammatory arthritis not defined. We report here that is up-regulated synovial membrane fluid...
Abstract Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic infection allergic disorders. CD4+ T cells which produce type can be generated via IL-4-dependent -independent pathways. Although the pathway is well documented, factors that drive IL-4-independent Th2 cell differentiation remain obscure. We report here new cytokine IL-33, presence of Ag, polarizes murine human naive into population mainly IL-5 but not IL-4. This polarization requires IL-1R-related molecule...
IL-33, a cytokine of the IL-1 family, is closely associated with type II T cell responses. Here, we report an unexpected proinflammatory role IL-33 in inflammatory arthritis. was expressed synovial fibroblasts from patients rheumatoid arthritis (RA). Expression markedly elevated vitro by cytokines. Mice lacking ST2, receptor α-chain, developed attenuated collagen-induced (CIA) and reduced ex vivo collagen-specific induction cytokines (IL-17, TNFα, IFNγ), antibody production. Conversely,...
Although microRNA (miRNA) regulation of TLR signaling is well established, this has not yet been observed for NLR proteins or the inflammasomes they form. We have now validated a highly conserved miR-223 target site in NLRP3 3'-untranslated region. expression decreases as monocytes differentiate into macrophages, whereas protein increases during time. However, overexpression prevents accumulation and inhibits IL-1β production from inflammasome. Virus inhibition inflammasome an emerging...
The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs patients with idiopathic fibrosis.We aimed to determine effects mechanism IL-33 on development severity murine bleomycin-induced fibrosis.Lung was induced by bleomycin wild-type or Il33r (St2)(-/-) C57BL/6 mice treated recombinant mature form anti-IL-33 antibody transferred type 2 innate lymphoid cells (ILC2s). evaluated based lung...
Abstract IL-33 has emerged as an important mediator in the immunopathogenesis of allergy and asthma. However, role eosinophil-mediated inflammation not been fully explored. In this article, we report that directly stimulates eosinophil differentiation from CD117+ progenitors IL-5–dependent manner. Although resting eosinophils expressed moderate levels IL-33R α-chain (ST2L), accumulated airways mice with OVA-induced asthma increased amounts ST2L. vitro, GM-CSF are potent inducers ST2L...
Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in mammalian genomes, and yet, their functions remain largely unknown. As part FANTOM6 project, we systematically knocked down expression 285 lncRNAs human dermal fibroblasts quantified cellular growth, morphological changes, transcriptomic responses using Capped Analysis Gene Expression (CAGE). Antisense oligonucleotides targeting same exhibited global concordance, molecular phenotype, measured by CAGE, recapitulated...
Abstract Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTK low CD48 + macrophages LYVE1 MRC1+ enriched for negative regulators of inflammation co-exist in frozen capsule tissues. Micro-cultures patient-derived cells integrin-mediated cell-matrix interactions between MERTK+ pro-resolving DKK3+...
Abstract MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing common human condition tendinopathy as a model system to explore immediate inflammation matrix synthesis by miRNA we observed that elevated IL-33 expression is characteristic early tendinopathy. Using in vitro tenocyte cultures vivo models tendon damage, demonstrate such plays pivotal role transition from type 1 3 collagen...
Pathogenic mycobacteria, including Mycobacterium tuberculosis and bovis, cause significant morbidity mortality worldwide. However, the vaccine strain bovis BCG, unlike virulent strains, triggers extensive apoptosis of infected macrophages, a step necessary for elicitation robust protective immunity. We here demonstrate that M. BCG Toll-like receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein...
Hepatic steatosis is a global epidemic that thought to contribute the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators can functionally integrate range metabolic and inflammatory pathways in liver. We aimed investigate functional role miR-155 hepatic steatosis. Male C57BL/6 wild-type (WT) miR-155(-/-) mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, parameters assessed livers serum mice. Mice lacking endogenous HFD developed increased...
Objective— Clinical studies have identified that reduced numbers of circulating plasmacytoid dendritic cells (pDCs) act as a predictor cardiovascular events in coronary artery disease and pDCs are detectable the shoulder region human atherosclerotic plaques, where rupture is most likely to occur. Results from animal models controversial, with seen inhibit or promote lesion development depending on experimental settings. Here, we investigated role atherosclerosis apolipoprotein E−deficient...
Abstract MicroRNA-155 (miR-155) is an important regulator of B cells in mice. have a critical role the pathogenesis rheumatoid arthritis (RA). Here we show that miR-155 highly expressed peripheral blood from RA patients compared with healthy individuals, particularly IgD - CD27 memory B-cell population ACPA + RA. MiR-155 synovial tissue containing ectopic germinal centres diffuse tissue. expression associated reciprocally lower PU.1 at level compartment. Stimulation donor CD40L, anti-IgM,...
Objective. To test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and receptor expression in RA, thereby is associated with disease activity. Methods. The copy-numbers monocytes from peripheral blood (PB) healthy (n = 22), RA 24) SF 11) were assessed by real time-PCR using synthetic as a quantitative standard. evaluate functional impact miR-155, human transfected control or mimic, effect on transcript levels, production chemokines was evaluated...
We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic resolving macrophage pathways their role in pathogenesis. found that bronchoalveolar lavage fluid (BALF) clusters FCN1+ FCN1+SPP1+ predominant severe were transcriptionally related to synovial tissue (STM) CD48hiS100A12+ CD48+SPP1+ drive rheumatoid (RA) synovitis. BALF cluster FABP4+ healthy lung was STM TREM2+ governs resolution of synovitis RA remission. Plasma concentrations SPP1 S100A12 (key...
To integrate published single-cell RNA sequencing (scRNA-seq) data and assess the contribution of synovial fibroblast (SF) subsets to pathotypes respective clinical characteristics in treatment-naïve early arthritis.In this silico study, we integrated scRNA-seq from studies with additional unpublished in-house data. Standard Seurat, Harmony Liger workflow was performed for integration differential gene expression analysis. We estimated single cell type proportions bulk RNA-seq...
Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and adaptive immunity. There is therefore intense interest the factors that integrate these immunologic pathways rheumatoid arthritis. In this paper, we report IL-33, a novel member of IL-1 family, can exacerbate anti-glucose-6-phosphate isomerase autoantibody-induced (AIA). Mice lacking ST2 (ST2(-/-)), IL-33 receptor alpha-chain, developed attenuated AIA reduced expression articular proinflammatory cytokines....
IL-33 is a new member of the IL-1 family, which plays crucial role in inflammatory response, enhancing differentiation dendritic cells and alternatively activated macrophages (AAM). Based on evidence expression bone, we hypothesized that may shift balance from osteoclast to AAM protect bone loss. Using transgenic mice overexpressing human TNF, develop spontaneous joint inflammation cartilage destruction, show administration or an IL-33R (ST2L) agonistic Ab inhibited systemic loss,...