A5008486711- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Allergic Rhinitis and Sensitization
- Dermatology and Skin Diseases
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Pediatric health and respiratory diseases
- Immunotherapy and Immune Responses
- NF-κB Signaling Pathways
- Lung Cancer Diagnosis and Treatment
- Antimicrobial Peptides and Activities
- Mast cells and histamine
- Food Allergy and Anaphylaxis Research
- Ion Channels and Receptors
- Epigenetics and DNA Methylation
- Adenosine and Purinergic Signaling
- Mining and Resource Management
- Lipid Membrane Structure and Behavior
- Estrogen and related hormone effects
- Air Quality and Health Impacts
- Vitamin D Research Studies
- Eosinophilic Disorders and Syndromes
University of Leicester
2015-2024
NIHR Leicester Biomedical Research Centre
2015-2024
National Institute for Health Research
2015-2023
University of Virginia
2022
King's College London
2009-2021
Asthma UK
2011-2021
Medical Research Council
2008-2021
NIHR Leicester Respiratory Biomedical Research Unit
2015-2021
University Hospitals of Leicester NHS Trust
2019
Guy's Hospital
1994-2018
Abstract Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma characterized by elevated bronchial mucosal TSLP and Th2-attracting, but not Th1-attracting, as compared with controls, selective accumulation cells bearing receptors for these chemokines. used in situ hybridization immunohistochemistry examine the cellular provenance TSLP, Th2-attracting (thymus activation-regulated chemokine (TARC)/CCL17,...
Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms poorly understood. We hypothesized that epithelial cell-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation type 2 inflammation.To assess whether rhinovirus induces inflammatory response vivo and to define for this pathway.We used human experimental model infection novel airway sampling techniques measure IL-4, IL-5, IL-13, levels asthmatic healthy airways...
Abstract Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of cells secretion chemokines which preferentially attract them. We hypothesized that there is distinct airways expression TSLP Th1- Th2-type cells, influx bearing their receptors in asthma COPD. In situ hybridization, immunohistochemistry, ELISA were used to examine the cellular provenance TSLP,...
IL-25 critically links rhinovirus infection and allergic asthma exacerbations.
Signaling through the TLR family of molecular pattern recognition receptors has been implicated in induction innate and adaptive immune responses. A role for signaling maintenance and/or regulation Treg function proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human secreting antiinflammatory cytokine IL-10 induced following stimulation blood tissue CD3+ T cells presence 1α,25-dihydroxyvitamin D3 (1α25VitD3), active form Vitamin...
Phenotypic modulation of airway smooth muscle (ASM) is an important feature remodeling in asthma that characterized by enhanced proliferation and secretion pro-inflammatory chemokines. These activities are regulated the concentration free Ca(2+) cytosol ([Ca(2+)](i)). A rise [Ca(2+)](i) normalized rapid reuptake into sarcoplasmic reticulum (SR) stores sarco/endoplasmic (SERCA) pump. We examined whether increased proliferative secretory responses ASM from asthmatics result reduced SERCA...
Interleukin-23 has been implicated in airway inflammation that is mediated by type 2 and 17 cytokines. Whether targeting interleukin-23 the treatment of asthma improves disease control reduces unclear.We conducted a phase 2a, multicenter, randomized, double-blind, placebo-controlled, 24-week, parallel-group trial to assess efficacy safety risankizumab, an anti-interleukin-23p19 monoclonal antibody, adults with severe asthma. Patients were assigned receive 90 mg risankizumab or placebo,...
Abstract We have developed an in vitro differentiation assay which human naive CD4+ cells are driven toward either the Th1 or Th2 phenotype. examined interrelationships among expression of IL-2, IL-4, IL-5, IL-10, IL-13, GM-CSF, and IFN-γ individual using intracellular cytokine staining at various times during process. provide direct evidence that cytokines unlike other cytokines, regulated by a coordinated mechanism. also show IL-10 is expressed different subset prevalent early stages...
BackgroundChronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 IL-13 response to IL-25 IL-33, although the relevance of this axis local mucosal T-cell responses unknown.ObjectiveWe sought investigate role IL-25/IL-33 patients CRSwNP.MethodsPolyp tissue blood were obtained undergoing polypectomy. Control biopsy specimens healthy volunteers....
Abstract Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged Ag-specific receptors, although many soluble factors such as cytokines mediators can influence ILC2, direct interaction of these with the microenvironment other has been less explored. Natural cytotoxicity receptors expressed by subsets group 1 ILC 3 thought to be their function, but they have...
Newly characterized type 2 innate lymphoid cells (ILC2s) display potent effector functionality; however, their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used characterize the airway mucosa invasive, tolerated, does not allow for sequential sampling.To assess role of ILC2s during nasal allergen challenge in subjects with rhinitis using novel noninvasive methodology.We a human experimental model, flow cytometric analysis curettage samples,...
Background Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, vitamin D insufficiency, compromises immune regulation, are detrimental in asthma. Objectives Mechanistic cell culture experiments were undertaken to ascertain whether abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement antioxidant pathways. Methods Transcriptome analysis, PCR ELISA delineate markers inflammation stress; with...
Human skin–derived ILC2 express CD1a and present endogenous PLA2G4A-dependent antigens to T cells.
Abstract The differentiation of naive CD4+ T lymphocytes into Th1 and Th2 lineages generates either cellular or humoral immune responses. cells express the cytokines IL-4, -5, -13, which are implicated in asthma atopy. Much has been published about regulation murine cytokine expression, but studies human primary less common. We have developed a method for differentiating CD45RA+ (naive) populations that display distinct expression profiles. examined both CpG methylation, using bisulfite DNA...
Highlights•Th1 genes and Th2 are associated with RNA pol II in the alternative lineage•T-bet acts to recruit Mediator SEC activate Th1 eRNAs•T-bet NF-κB-dependent P-TEFb recruitment pathways converge at enhancers•P-TEFb inhibition silences T-bet target abrogates uveitis vivoSummaryThe transcription factor directs cell differentiation, but molecular mechanisms that underlie this lineage-specific gene regulation not completely understood. Here, we show through enhancers allow of form super...
Glucocorticoids are the mainstay of asthma therapy and mediate repression a number cytokine genes, such as Interleukin (IL)-4, -5, -13, granulocyte macrophage colony-stimulating factor (GM-CSF), which central to pathogenesis asthmatic airway inflammation. The glucocorticoid receptor (GR) mediates by diverse mechanisms. We have previously suggested that one repressive activity is direct binding GR elements within GM-CSF enhancer recognized nuclear activated T cells.activator protein 1...
Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one the most characteristic features remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested affect by stimulation human cell proliferation.To investigate effect S1P on signalling regulation gene expression from healthy asthmatic individuals.Airway grown bronchial biopsies individuals were exposed S1P. Gene was analysed using microarray, real-time...
BackgroundRepeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy.ObjectiveWe sought to evaluate the efficacy safety of immunotherapy in treatment allergic rhinitis.MethodsWe randomly assigned 93 adults pollen–induced rhinitis receive 7 preseasonal injections (containing ng Phl p 5 major allergen) or a histamine control. The primary end point was daily...
Rationale: Type 2 innate lymphoid cells (ILC2s) are significant sources of type cytokines, which implicated in the pathogenesis asthma and exacerbations. The role ILC2s virus-induced exacerbations is not well characterized. Objectives: To characterize pulmonary ILC responses following experimental rhinovirus challenge patients with moderate healthy subjects. Methods: Patients subjects were inoculated rhinovirus-16 underwent bronchoscopy at baseline Day 3, 8 after inoculation. Pulmonary ILC1s...
Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver some asthma phenotypes.To derive gene signatures from in vitro studies IL-33-stimulated cells use these to determine IL-33-associated enrichment patterns asthma.Signatures downstream IL-33 stimulation were derived our study human mast public datasets stimulated basophils, innate lymphoid (ILC2), regulatory T (Treg) endothelial cells. Gene Set Variation Analysis (GSVA)...