A5006935754- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Inflammatory Bowel Disease
- T-cell and B-cell Immunology
- Gut microbiota and health
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Spondyloarthritis Studies and Treatments
- Eosinophilic Esophagitis
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Microscopic Colitis
- Dermatology and Skin Diseases
- Digestive system and related health
- Epigenetics and DNA Methylation
- Infant Nutrition and Health
- Helicobacter pylori-related gastroenterology studies
- Clostridium difficile and Clostridium perfringens research
- Parasites and Host Interactions
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Immune responses and vaccinations
- Nutrition and Health in Aging
- Clinical Nutrition and Gastroenterology
University of Glasgow
2016-2025
Versus Arthritis
2019-2024
Institute of Infection and Immunity
2013-2024
Glasgow Royal Infirmary
2022
Royal Hospital for Sick Children
2021
Royal Hospital for Children
2021
Glasgow Life
2020
University of Oxford
2004-2011
Hospital Universitario La Paz
2011
The Rotherham NHS Foundation Trust
2010
Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications the modulation of intestinal immune responses have never studied. The aim this study was to investigate role ileal bacteria modulating local and systemic AS.Ileal biopsies were obtained from 50 HLA-B27+ AS 20 normal subjects. Silver stain used visualise bacteria. Ileal expression tight adherens junction proteins investigated by TaqMan real-time (RT)-PCR immunohistochemistry. Serum...
Background & AimsExclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability limited. There a need novel treatments CD.MethodsWe evaluated effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on gut microbiome, inflammation, and clinical response in rat model, healthy adults, children relapsing CD. Twenty-five adults randomly received EEN or CD-TREAT 7 days, followed by 14-day washout period,...
Macrophages in the healthy intestine are highly specialized and usually respond to gut microbiota without provoking an inflammatory response. A breakdown this tolerance leads bowel disease (IBD), but mechanisms by which intestinal macrophages normally become conditioned promote microbial unclear. Strong epidemiological evidence linking disruption of antibiotic use early life IBD indicates important role for modulating immunity. Here, we show that causes hyperresponsive bacterial stimulation,...
Highlights•ZEB2 is highly expressed across the macrophage lineage•ZEB2 preserves tissue-specific identities of macrophages tissues•ZEB2 deficient are outcompeted by WT counterparts•LXRα crucial for Kupffer cell identity and maintained ZEB2SummaryHeterogeneity between different populations has become a defining feature this lineage. However, conserved factors remain largely unknown. The transcription factor ZEB2 best described its role in epithelial to mesenchymal transition; however, within...
Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control CD4 T-cell responses to commensal bacteria. It not known whether ILC populations migrate from their mucosal and peripheral sites local draining secondary tissues. Here we demonstrate that ILC3s reside the interfollicular areas lymph nodes, forming a distinct microenvironment observed in nodes. By photoconverting intestinal Kaede mice reveal...
The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature origins CD103(-) MPs remain controversial. We show here that CD103(-)CD11b(+) can separated clearly into DCs mφs based on phenotype, gene profile, kinetics. CD64(-)CD103(-)CD11b(+) are classical being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C(hi) monocytes. Surprisingly,...
Intestinal macrophages (mφ) form one of the largest populations mφ in body and are vital for maintenance gut homeostasis. They have several unique properties derived from local differentiation classical Ly6Chi monocytes, but factors driving this tissue-specific process not understood. Here we used global transcriptomic analysis to identify a homeostatic signature mature colonic that is acquired as they differentiate mucosa. By comparing analogous monocyte found dermis, TGFβ an indispensable...
T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, DC subpopulations that induce Th2 in intestine unidentified. Here we show intestinal Trichuris muris worms and Schistosoma mansoni eggs do not develop mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer conventional DCs, particular CD11b-expressing from intestine, is sufficient to prime S. mansoni-specific responses. Surprisingly,...
Cross-presentation of cellular antigens is crucial for priming CD8+ T cells, and generating immunity to intracellular pathogens—particularly viruses. It unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the lymph IFABP-tOVA 232-4 mice, express ovalbumin small epithelial (IECs). Among DCs (LDCs) only CD103+ CD11b− CD8α+ cross-present IEC-derived OT-I cells. Similarly, mesenteric nodes (MLNs), cross-presentation...
Osteoarthritis (OA) is a leading cause of disability, globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target therapeutically have had limited success. A better understanding the cellular and molecular processes occurring synovium needed develop novel therapeutics. We investigated macrophage phenotype gene expression tissue inflammatory-arthritis (IA) patients. Compared with IA, contained higher but variable proportions macrophages (P < 0.001)....
Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+ NKG2D+ T cells dominate follicle pathogenesis, but specific mechanisms driving are not fully understood.To provide detailed insight into systemic cytokine signature associated with AA, and assess association between cytokines depression.We conducted multiplex analysis of plasma from patients psoriatic arthritis (PsA) healthy...
Summary Background Exclusive enteral nutrition (EEN) is an effective treatment for Crohn's disease. Aims To investigate the hypothesis that ingredients of EEN formulas are unlikely to initiate a disease flare and their dietary elimination not essential amelioration. Methods We performed compositional analysis with evidence efficacy in management active Macronutrient content was compared against reference values (DRV), UK National Diet Nutrition Survey (NDNS) intake children. Food additives...
The gut microbiota's function in regulating health has seen it linked to disease progression several cancers. However, there is limited research detailing its influence breast cancer (BrCa). This study found that antibiotic-induced perturbation of the microbiota significantly increases tumor multiple BrCa mouse models. Metagenomics highlights common loss bacterial species following antibiotic administration. One such bacteria,
Inflammatory bowel disease (IBD) is a multifactorial disease, and patients frequently experience extraintestinal manifestations affecting multiple sites. Causes of systemic inflammation remain poorly understood, but molecules originating from the intestine likely play role, with microbial host small polarizing immune cells towards pro- or anti-inflammatory phenotype. Using dextran sodium sulfate (DSS) mouse model, which mimics disrupted barrier function, dysbiosis, cell dysregulation IBD, we...
Abstract Dendritic cells (DCs) migrating via lymph are the primary influence regulating naive T cell differentiation, be it active immunity or tolerance. How DCs achieve this regulation in vivo is poorly understood. Intestinal direct contact with harmless pathogenic luminal contents, but may also influenced by signals from epithelial cells, macrophages, other resident immigrant cells. To understand role of TLR7 and TLR8 intestinal DC function, we fed a TLR7/8 ligand (resiquimod (R-848)) to...
Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance pathogenesis by activating auto-reactive lymphocytes. Here we show microRNA-34a provides homoeostatic control CD1c+ DC activation via regulation tyrosine kinase receptor AXL, an important inhibitory auto-regulator. This pathway is in DCs from patients with upregulation...
Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal changes food re-introduction and the influence of maintenance nutrition.To study to at reintroduction, explore associations nutrition.Children disease were followed food-reintroduction. was measured before, 33 54 days nutrition, 17, 52 72 after Maintenance use recorded estimated weight diaries. Data are presented medians Q1:Q3.Sixty-six patients started 41 (62%)...
Discovery of novel bacterial metabolites reveals an unprecedented role for the microbiome in gut-brain axis communication.