A5049364696- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- T-cell and B-cell Immunology
- Inflammatory Bowel Disease
- Respiratory viral infections research
- Asthma and respiratory diseases
- Vagus Nerve Stimulation Research
- Nicotinic Acetylcholine Receptors Study
- Immunotherapy and Immune Responses
- Pediatric health and respiratory diseases
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Neonatal Respiratory Health Research
- Glycosylation and Glycoproteins Research
- Animal Genetics and Reproduction
- Immunodeficiency and Autoimmune Disorders
- Wine Industry and Tourism
- Escherichia coli research studies
- Action Observation and Synchronization
- Mast cells and histamine
- CRISPR and Genetic Engineering
Manchester Academic Health Science Centre
2023-2025
University of Manchester
2023-2025
King's College London
2018-2024
Imperial College London
2016-2022
National Institute for Health Research
2021
NIHR Biomedical Research Centre at The Royal Marsden and the ICR
2021
University of Bristol
2015
Vehicle Technologies Office
2009
Philadelphia University
2008
California State University, Sacramento
2001
Synthesis of acetylcholine by group 2 innate lymphoid cells is important for optimal immune responses to helminth infection.
Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance high intracellular cAMP concentration. A number microRNAs are implicated the Tregs. In this study, we demonstrate that peripheral critically posttranscriptional repression cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). manner, miR-142-5p acts as an immunometabolic regulator cAMP, controlling Treg suppressive...
Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components immune response. carried out loss gain function studies establish if required for optimal parasite. N. infection SP-D-/- mice resulted profound impairment host innate...
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, intestinal pulmonary organoids harnessed to demonstrate that the epithelial niche is sufficient drive tissue-specific all (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex induced pluripotent stem (hiPSC)-based gut lung organoid used cells recapitulate ILC from a stringent systemic ILCP population, but only when...
The nematode parasite Angiostrongylus vasorum is an increasingly important cause of respiratory and other diseases in dogs. Geographical spread from previously limited endemic foci has occurred rapidly. This paper investigates epidemiology around the location first reported case Scotland 2009: by detection A ‐specific DNA gastropod intermediate hosts, dogs circulating specific antibodies, stage larvae faeces. Overall prevalence gastropods was 6.7 per cent (16/240), with found slugs Arion...
Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising biological effects of these molecules. We describe here novel system for heterologous expression helminth secreted proteins in natural parasite mice, Trypanosoma musculi, can be used analyse putative immunomodulatory functions. Trypanosomes were engineered express acetylcholinesterase from Nippostrongylus brasiliensis....
Airway inflammation and remodelling are important pathophysiologic features in asthma other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, this depends on intercellular adhesion, whilst damaged epithelium the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) highly expressed where it modulates cell-cell adhesion stability facilitates immune transepithelial migration. However, contribution CAR remains...
The mouse cell line MOPC 315 is an IgA (lambda II)-producing myeloma. We have studied a derivative of that secretes normal lambda II chains but no heavy chain. This derivative, 315-26, was found to contain rearranged I gene in addition gene. cloned into bacteriophage DNA and its structure studied. arisen by aberrant recombination event resulted single base insertion at the site V-J region joining. In addition, contained numerous point mutations vicinity junction V J regions. Two occurred...
Abstract Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate (ILC2s) being particularly important in type immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role homeostasis and function ILC2s. Mice deficient for miR-142 expression an ILC2 progenitor–biased development bone marrow, along peripheral ILC2s these display greatly altered phenotype based on surface marker expression....
Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet + CD127 group 1 (ILC1) have been linked to pathogenesis of human inflammatory bowel disease (IBD). However, functional importance ILC1 context an intact adaptive has controversial. In this report we demonstrate that induced depletion using Rosa26-Cre-ERT2 model resulted loss ILC1, pointing post-developmental requirement expression for these cells. contrast, neither colonic lamina propria (cLP)...
Innate lymphoid cells (ILCs) are tissue-resident effector with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type modules exhibit significant ontological, transcriptional, phenotypic, functional heterogeneity. Notably inducer (LTi)-like ILC3s mediate functions not typically associated other RORγt-expressing...
Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and unrelated triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators so far not been tested virus-induced disease. We now report AvCystatin prevents Th2-based immunopathology...
Type-3 innate lymphoid cells (ILC3) respond to localized environmental cues regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator downstream target of ILC3 signaling, however, complexity mucosal tissues can hinder efforts define specific interactions between these two compartments. Here, we employ a reductionist co-culture system murine epithelial small organoids (SIO) with uncover bi-directional signaling mechanisms that...
Differential responsiveness to interleukin [IL]-2 between effector CD4+ T cells [Teff] and regulatory [Treg] is a fundamental mechanism of immunoregulation. The single nucleotide polymorphism [SNP] rs61839660, located within IL2RA [CD25], has been associated with the development Crohn's disease [CD]. We sought identify cell immune phenotype IBD patients who carry this SNP.Teff Treg were isolated from individuals homozygous [TT], heterozygous [CT], or wild-type [CC] for minor allele at used...
Organ transplantation is often lifesaving, but the long-term deleterious effects of combinatorial immunosuppression regimens and allograft failure cause significant morbidity mortality. Long-term graft survival in absence continuing immunosuppression, defined as operational tolerance, has never been described context multiple major histocompatibility complex (MHC) mismatches. Here, we show that miR-142 deficiency leads to indefinite a fully MHC mismatched murine cardiac transplant model...
Abstract The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface gut microbiome and mucosal immunity, adaptive innate lymphoid populations regulate balance between commensal micro-organisms pathogens. Checkpoint inhibitors, particularly those targeting CTLA-4 pathway, disrupt this fine can lead to inflammatory bowel disease immune checkpoint colitis. Here, we show that expressed by cells its expression regulated ILC...
Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses is associated with development several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh required for optimal type to parasitic infection therefore sought determine whether this also a allergic inflammation. Rora Cre+ Chat LoxP mice (in which ILC2s cannot synthesize ACh) were exposed allergenic extract fungus...