A5053622449- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Cancer Immunotherapy and Biomarkers
- Irish and British Studies
- Immunodeficiency and Autoimmune Disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immune Response and Inflammation
- CAR-T cell therapy research
- Atherosclerosis and Cardiovascular Diseases
- Diverse Musicological Studies
- IL-33, ST2, and ILC Pathways
- Historical Art and Culture Studies
- Chemokine receptors and signaling
- Cell death mechanisms and regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Joseph Conrad and Literature
- Archaeology and ancient environmental studies
- Archaeological Research and Protection
- NF-κB Signaling Pathways
- Eosinophilic Esophagitis
- Blood disorders and treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
The Royal Free Hospital
2014-2024
University College London
2015-2024
Manchester Metropolitan University
2024
Queen Mary University of London
2024
Institute of Infection and Immunity
2020-2023
The London College
2023
Imperial College London
2023
University of Manchester
2023
Dorset County Hospital
2022
Roland Hill (United Kingdom)
2013-2018
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of cell immune responses whose mechanism action the subject debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that can capture its from opposing cells by process trans-endocytosis. After removal, these costimulatory are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via Acquisition CD86 antigen-presenting stimulated receptor engagement...
The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment infectious disease autoimmune conditions. A variety immune cells, including macrophages, dendritic activated T cells express intracellular D receptor are responsive to 1,25(OH)(2)D(3.) Despite this, how 1,25(OH)(2)D(3) regulates adaptive immunity remains unclear may involve both direct indirect effects on...
The failure of CD25+ regulatory T cells (Tregs) to proliferate after cell receptor (TCR) stimulation in vitro has lead their classification as naturally anergic. Here we use Tregs expressing a transgenic TCR show that despite anergy vitro, response immunization vivo. also and accumulate locally transgenically expressed tissue antigen whereas CD25− counterparts are depleted at such sites. Collectively, these data suggest the anergic state characterizes may not accurately reflect...
CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation inhibition of responses, respectively. Although both receptors share same ligands, CD80 CD86, specific requirement for two distinct ligands remains obscure. In present study, we demonstrate that, although targets CD86 destruction via transendocytosis, this process results separate fates itself. presence CD80, remained ligand bound, was ubiquitylated trafficked late endosomes lysosomes....
Abstract CD4+CD25+Foxp3+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance by inhibiting expansion and function conventional cells. Treg development homeostasis are regulated Ag receptor, costimulatory receptors such as CD28 CTLA-4, cytokines IL-2, IL-10, TGF-β. Here we show that proportions Tregs in spleen lymph nodes mice with inactive p110δ PI3K (p110δD910A/D910A) reduced despite enhanced selection thymus. p110δD910A/D910A showed attenuated suppressor vitro...
Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte–associated molecule 4–immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 cells, linked migration into B follicles. Germinal center formation restored CTLA4-Ig transgenic mice coinjection an agonistic monoclonal...
Genes that act inside the cell to negatively regulate proliferation are of great interest because their implications for such processes as development and cancer, but these genes have been difficult clone. This report details cloning analysis cDNA prohibitin, a novel mammalian antiproliferative protein. Microinjection synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts HeLa cells. an antisense oligonucleotide stimulates phase. By sequence comparison, gene appears...
Abstract Regulatory T cells (Tregs) are found at sites of chronic inflammation where they mediate bystander and Ag-specific suppression local immune responses. However, little is known about the molecular control Treg recruitment into inflamed human tissues. We report that up to 18% in areas liver disease forkhead family transcriptional regulator box P3 (FoxP3)+ Tregs. isolated CD4+CD25+CD127lowFoxP3+ Tregs from chronically removed transplantation; compared with blood-derived Tregs,...
Mucosal tissues require constant immune surveillance to clear harmful pathogens while maintaining tolerance self Ags. Regulatory T cells (Tregs) play a central role in this process and expression of alpha(E)beta(7) has been reported define subset Tregs with tropism for inflamed tissues. However, the signals responsible recruiting epithelial surfaces are poorly understood. We have isolated CCR10-expressing CD25+CD4+Foxp3+ potent anti-inflammatory properties from chronically human liver. The...
Significance The inhibitory protein cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is recognized as a crucial regulator of autoimmunity, but its precise mechanism action not yet fully understood. CTLA-4 can down-regulate expression the costimulatory ligands CD80 and CD86 on antigen presenting cells, thereby reducing T-cell CD28 engagement. Here we demonstrate that quantitative changes in level engagement have functional consequences for differentiation toward follicular helper T cells...
The strong genetic association between particular HLA alleles and type 1 diabetes (T1D) indicates a key role for CD4+ T cells in disease; however, the differentiation state of responsible is unclear. cell originally was considered dichotomy Th1 Th2 cells, with deemed culpable autoimmune islet destruction. Now, multiple additional fates are recognized distinct roles. Here, we used transgenic mouse model to probe gene expression profile islet-specific by microarray identified clear follicular...
The CTLA-4 pathway is recognized as a major immune inhibitory axis and key therapeutic target for augmenting antitumor immunity or curbing autoimmunity. CTLA-4-deficient mice provide the archetypal example of dysregulated homeostasis, developing lethal lymphoproliferation with multiorgan inflammation. In this study, we show that surprisingly these have an enlarged population Foxp3(+) regulatory T cells (Treg). increase in Treg associated normal thymic output but enhanced proliferation...