A5034784907- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Respiratory and Cough-Related Research
- T-cell and B-cell Immunology
- Eosinophilic Esophagitis
- Inhalation and Respiratory Drug Delivery
- Tuberculosis Research and Epidemiology
- Pediatric health and respiratory diseases
- Respiratory viral infections research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Phagocytosis and Immune Regulation
- Mycobacterium research and diagnosis
- SARS-CoV-2 and COVID-19 Research
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- Pneumonia and Respiratory Infections
- Allergic Rhinitis and Sensitization
- Immune responses and vaccinations
- Infectious Diseases and Tuberculosis
- Gut microbiota and health
- Pleural and Pulmonary Diseases
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
University of Oxford
2008-2025
John Radcliffe Hospital
2007-2025
Oxford BioMedica (United Kingdom)
2018-2024
University Hospital Southampton NHS Foundation Trust
2015-2024
University of Southampton
2009-2024
NIHR Southampton Respiratory Biomedical Research Unit
2015-2024
National Institute for Health Research
2015-2024
Churchill Hospital
2022
Peter Doherty Institute
2015-2020
The University of Melbourne
2015-2020
Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune patients with TB suggest the presence of activity. CD4+CD25high T cells mediate immunity several chronic infections have not been described TB.Objective: To determine whether are increased they suppress responses.Methods: We compared frequency circulating 27...
Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation rapid accumulation of with immune detectable immunocompetent animals. is more evident mice...
Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity relationships to asthma severity are unclear.We performed comprehensive assessment of TH17 cells, regulatory T mucosal-associated invariant (MAIT) other T-cell subsets, granulocyte in asthmatic patients.Sixty patients with mild-to-severe 24 control subjects underwent detailed clinical provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, blood samples. Adaptive cytokines,...
Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like conserved across mammalian species, including mice and humans. By sequencing RNA from sorted MR1-5-OP-RU tetramer+ derived either human blood or murine lungs, we define the basic transcriptome of an activated MAIT cell in both species demonstrate how this profile changes during resolution infection reinfection. We observe strong similarities between humans mice. In activation leads to expression pro-inflammatory...
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT also activated during viral infections, yet it remains unknown whether play a significant protective or even detrimental role infections vivo. Using murine experimental challenge with two strains of influenza A virus, we show that accumulate early infection, upregulation CD25, CD69 Granzyme...
BackgroundAlthough several studies link high levels of IL-6 and soluble receptor (sIL-6R) to asthma severity decreased lung function, the role trans-signaling (IL-6TS) in asthmatic patients is unclear.ObjectiveWe sought explore association between epithelial IL-6TS pathway activation molecular clinical phenotypes patients.MethodsAn gene signature obtained from air-liquid interface cultures human bronchial cells stimulated with sIL-6R was used stratify transcriptomic data (Unbiased Biomarkers...
Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses contribute to protection. We hypothesized that MAIT may have inherent adjuvant activity in vaccine platforms use replication-incompetent adenovirus vectors. In mice humans, ChAdOx1 (chimpanzee Ox1) immunization robustly activated cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α monocyte-derived interleukin-18. IFN-α-induced, tumor necrosis...
Reduction of the risk asthma attacks is a major goal current management. We propose to derive scale predicting based on blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted pooled from control arms Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 DREAM trials (n=3051). These used rate ratios predicted for different patient groups. The resultant prototype shows potential predict attacks, which may be...
Clinical risk factors for severe asthma attacks have been identified, but their incremental prognostic values are unclear. Additionally, the contribution of type 2 inflammation, a common, treatable process, is undetermined. We aimed to quantify value baseline characteristics and inflammatory biomarkers, specifically blood eosinophil count fractional exhaled nitric oxide (FeNO), predict attacks. In this systematic review meta-analysis randomised controlled trials (RCTs), Oxford Asthma Attack...
Abstract Distinct IFN-γ and IL-2 profiles of Ag-specific CD4+ T cells have recently been associated with different clinical disease states Ag loads in viral infections. We assessed the kinetics functional profile Mycobacterium tuberculosis secreting 23 patients untreated active when bacterial are high after curative treatment, load is reduced. The frequencies M. IFN-γ-secreting declined during 28 mo follow-up an average percentage decline 5.8% per year (p = 0.005), while IL-2-secreting...
Background: The role of new T-cell–based blood tests for tuberculosis in the diagnosis active is unclear. Objective: To compare performance 2 interferon-γ assays and tuberculin skin testing adults with suspected tuberculosis. Design: Prospective study conducted routine practice. Setting: urban hospitals United Kingdom. Patients: 389 adults, predominantly South Asian black ethnicity, moderate to high clinical suspicion Intervention: Tuberculin testing, enzyme-linked immunospot assay (ELISpot)...
In this study, we sought to determine whether asthma has a metabolic profile and is related disease severity. We characterised the serum from 22 healthy individuals 54 asthmatics (12 mild, 20 moderate, severe) using liquid chromatography–high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted spectrometry assays of eicosanoids, sphingolipids free fatty acids. conclusively identified 66 metabolites; 15 significantly altered with (p≤0.05). Levels...
Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive disease (COPD) exacerbations and plausible target for MAIT cells.To investigate whether respond to NTHi effects of inhaled corticosteroids (ICS) on their frequency function COPD.Eleven subjects COPD receiving ICS, 8 steroid-naive COPD, 21...
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment epithelium airway T cells that remain understudied asthma investigate interactions between multiple Epithelial brushings flow-sorted CD3+ sputum BAL were obtained healthy subjects (n = 19) patients with (mild, moderate, severe asthma; n 46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips, results...
Highlights•Hypoxia downregulates SARS-CoV-2 receptors ACE2 and TMPRSS2 inhibits viral entry•Hypoxic signaling replication particle genesis via HIF-1α•HIF prolyl hydroxylase inhibitors are a potential therapeutic option for COVID-19SummaryCOVID-19, caused by the novel coronavirus SARS-CoV-2, is global health issue with more than 2 million fatalities to date. Viral shaped cellular microenvironment, one important factor consider oxygen tension, in which hypoxia inducible (HIF) regulates...