A5047246825- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Allergic Rhinitis and Sensitization
- Contact Dermatitis and Allergies
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Inflammasome and immune disorders
- Urticaria and Related Conditions
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Atherosclerosis and Cardiovascular Diseases
- Autoimmune and Inflammatory Disorders Research
- Food Allergy and Anaphylaxis Research
- Autoimmune Bullous Skin Diseases
- Mast cells and histamine
- Immunodeficiency and Autoimmune Disorders
- Spondyloarthritis Studies and Treatments
- Nail Diseases and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Heat shock proteins research
NIHR Leeds Musculoskeletal Biomedical Research Unit
2015-2024
University of Leeds
2014-2024
University Medical Center of the Johannes Gutenberg University Mainz
2022-2024
Johannes Gutenberg University Mainz
2022-2024
Chapel Allerton Hospital
2013-2022
Leeds Teaching Hospitals NHS Trust
2013-2022
National Institute for Health Research
2013-2022
Bradford Teaching Hospitals NHS Foundation Trust
2012-2022
University of Pisa
2021
Cells Therapy (Poland)
2021
Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) 2‒mediated disorders humoral autoimmune pattern diseases, using VigiBase, World Health Organization's global pharmacovigilance adverse drug reactions. Several bioinformatics databases repositories...
Abstract There is increasing evidence that histamine as an important mediator of immediate type allergic reactions also effects professional APCs. Recent reports showed on human monocyte-derived dendritic cells (MoDC) mediated primarily via H1 receptors (H1R) and H2R. We show here MoDC express H3R H4R at the mRNA protein level. down-regulated up-regulated during differentiation from monocytes to MoDC. or H2R stimulation suppressed IL-12p70 production in Induction cAMP was necessary for...
<b><i>Objective:</i></b> We compared ultrasonography (US) with the modified nail psoriasis severity index (mNAPSI) to investigate plate, matrix and adjacent tendons in subjects psoriatic disease test hypothesis that involvement was specifically linked extensor tendon enthesopathy. <b><i>Methods:</i></b> 86 patients (169 nails) 20 healthy controls (HC) (40 were assessed both mNAPSI US. The thickness of region physical examination findings....
Significance IL-36γ is a potent cytokine that drives and orchestrates inflammation. It strongly expressed at barrier tissues such as the skin thus particularly relevant to inflammatory diseases affect these tissues, including psoriasis. an inactive precursor requires precise N-terminal truncation for activation. In investigations, we demonstrate cathepsin S major IL-36γ–activating protease by tissues. Moreover, show both are up-regulated in psoriatic These findings important they identify...
Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases been identified as promising drugs in chronic inflammatory disorders. Although many such developed, their introduction clinic has hampered by narrow therapeutic window with side effects nausea and emesis occurring at sub-therapeutic levels. The latest generation selective for...
Abstract Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have crucial role the progression to established autoimmune diseases. The cellular source and regulation disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells been thought contribute excessive type interferon production. Here, we show that autoimmunity systemic lupus erythematosus, are effector cells, lost capacity for...
Objective To evaluate clinical, interferon and imaging predictors of progression from ‘At Risk’ to autoimmune connective tissue diseases (AI-CTDs). Methods A prospective observational study was conducted in At-Risk AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months treatment-naïve). Bloods skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously...
We investigated whether the normal human spinal enthesis contained resident myeloid cell populations, capable of producing pivotal proinflammatory cytokines including tumour necrosis factor (TNF) and interleukin (IL)-23 determined these could be modified by PDE4 inhibition.Normal soft tissue (ST) adjacent perientheseal bone (PEB) (n=15) were evaluated using immunohistochemistry (IHC), digested for phenotyping, sorted stimulated with different adjuvants (lipopolysaccharide mannan). Stimulated...
The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses skin to rituximab are variable. This study was undertaken determine the phenotype rituximab-responsive disease.Eighty-two patients with SLE who were receiving prospectively studied. Of these patients, 32 had significant involvement before or after treatment. Disease activity assessed using British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous subtype classified by a dermatologist as...
The interleukin-36 receptor antagonist (IL-36Ra) which regulates IL-36α, -β and -γ is linked to psoriatic inflammation, especially loss-of-function mutations in pustular psoriasis subtypes. As observed with other IL-1 superfamily proteins, the IL-36 members require N-terminal cleavage for full biological activity but mechanisms of IL-36Ra activation remain poorly defined. Using different blood leukocyte skin resident cell preparations, recombinant we have identified that neutrophil elastase,...
Abstract Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity ISG transcriptome, cell-specific expression, response IFN-subtypes bimodality expression. We developed clinically validated a 2-score system (IFN-Score-A -B) using Factor Analysis 31 ISGs measured TaqMan selected from 3-IFN-annotated modules. evaluated these...
The human enthesis conventional T cells are poorly characterised.To study the biology of in enthesis.CD4+ and CD8+ were investigated 25 samples using immunofluorescence, cytometrically, bulk RNAseq quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires characterised a search for putative reactivity was carried out TCR3 database. impact pharmacological antagonism with retinoic...
Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30-60% of S. strains isolated from patients with AD are able to produce exotoxins superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA-D) toxic shock syndrome toxin-1 (TSST-1). Recently, it was demonstrated that the presence IgE antibodies SEA SEB is correlated severity skin lesions children AD. To determine relevance adult AD, we investigated relationship...
Objective To investigate whether sonographically determined subclinical enthesopathy in patients with moderate‐to‐severe psoriasis regresses the use of ustekinumab therapy for skin disease. Methods Seventy‐three psoriasis, who were not treated systemic and did have symptoms psoriatic arthritis (PsA), 23 healthy volunteers screened by ultrasound enthesitis. Subsequently, whose results showed inflammatory changes 52 weeks. The evolution sonographic abnormalities upper lower limb entheses was...
The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks which involve activation both resident and infiltrating inflammatory myeloid cells, aberrant angiogenesis. This research demonstrates a role for We show that induces production psoriasis-associated cytokines from macrophages (IL-23, TNFα) this response enhanced psoriasis patients. effect specific could not be mimicked by other such IL-1α. was also demonstrated to induce...
Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic psoriatic skin inflammation. known to induce inflammatory responses in dendritic cells, fibroblasts and Although vascular alterations hallmark lesions dermal endothelial cells well play critical role inflammation, the effects on unexplored. We here show that including microvascular express functionally active receptor. Adhesion molecules...
Abstract Human plasmacytoid dendritic cells (pDCs) play a vital role in modulating immune responses. They can produce massive amounts of type I IFNs response to nucleic acids via TLRs, but they are also known possess weak Ag-presenting properties inducing CD4+ T cell activation. Previous studies showed cross-regulation between TNF-α and IFN-α, many questions remain about the effect regulating human pDCs. In this study, we that significantly inhibited secretion IFN-α TLR-stimulated Instead,...