Publications by authors named "Christopher Dominic Buckley"
Article Synopsis
- Immune-mediated inflammatory diseases (IMIDs) significantly contribute to global health care costs and disease burden, often requiring complex management across different medical specialties.
- Many patients have overlapping IMIDs, suggesting shared mechanisms and potential for unified treatment approaches, as similar drugs are used across different conditions.
- A cellular, tissue-based understanding of inflammation could facilitate cross-disease clinical trials, improving drug development efficiency by evaluating treatments for multiple IMIDs simultaneously.
Objectives: The severity of skin involvement in diffuse cutaneous systemic sclerosis (dcSSc) depends on stage of disease and differs between anti-RNA-polymerase III (ARA) and anti-topoisomerase antibody (ATA) subsets. We have investigated cellular differences in well-characterised dcSSc patients compared with healthy controls (HCs).
Methods: We performed single-cell RNA sequencing on 4 mm skin biopsy samples from 12 patients with dcSSc and HCs (n=3) using droplet-based sequencing (10× genomics).
Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipo-cytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways.
View Article and Find Full Text PDFObjectives: To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.
Methods: 144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes.
Objectives: Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA).
Methods: Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display.
Article Synopsis
- The PI3Kδ protein helps control how certain immune cells, like B cells, work and can be important in fighting some blood cancers.
- Sjögren's syndrome is a disease where the immune system attacks glands, especially salivary glands, causing problems like dry mouth and tiredness.
- Blocking PI3Kδ with a specific medicine reduced harmful immune cell buildup in lab mice, suggesting this could be a new way to help treat Sjögren's syndrome.
Objectives: Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment.
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- - Tissue fibrosis and reduced blood vessel density are major issues in kidney disease, with CD248 being a protein linked to these problems in cells of damaged kidneys.
- - In a study using a kidney injury model, researchers found that mice without the CD248 gene showed less fibrosis and reduced blood vessel loss after injury, possibly due to changes in how cells called pericytes behaved.
- - The findings suggest that targeting CD248 could help prevent kidney damage by altering the activity of harmful stroma cells, offering a potential therapeutic approach for kidney disease.