A5089980191- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Immunotherapy and Immune Responses
- Pancreatic function and diabetes
- Cancer Immunotherapy and Biomarkers
- Global Public Health Policies and Epidemiology
- Immune Response and Inflammation
- Diabetes Management and Research
- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Mesenchymal stem cell research
- Liver physiology and pathology
- Health and Conflict Studies
- Global Health and Surgery
Aston University
2017-2019
University of Birmingham
2010-2015
Bipar
2014
Medical Research Council
2010-2014
University of Oxford
2014
Immune Regulation (United Kingdom)
2010-2011
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 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 a key regulator of T cell activation and critical failsafe against autoimmunity. Although early models postulated that transduced negative signal, in vivo evidence suggests functions cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function appears be cell-extrinsic, has an ongoing paradox the field. expressed on conventional cells (Tconv) can mediate inhibitory function, it unclear why this fails manifest as...
Abstract The cytokine IL-21 is a potent immune modulator with diverse mechanisms of action on multiple cell types. in clinical use to promote tumor rejection and an emerging target for neutralization the setting autoimmunity. Despite its potential, biological actions are not yet fully understood full range effects this pleiotropic still being uncovered. In study, we identify novel role as inducer costimulatory ligand CD86 B lymphocytes. provides critical signals through T cell–expressed CD28...
Abstract The entry of autoreactive T cells into the pancreas is a critical checkpoint in development autoimmune diabetes. In this study, we identify role for B1 process using DO11 × RIP-mOVA mouse model. transgenic mice with islet-specific cells, but no B are primed pancreatic lymph node fail to enter pancreas. Reconstitution cell population by adoptive transfer permits extensive infiltration. Reconstituted traffic and modify expression adhesion molecules on vasculature, notably VCAM-1....
Abstract Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), thought to have distinct autoantigen targets. Whilst RF targets Fc region of antibodies, ACPAs target a far broader spectrum citrullinated peptides. Here we demonstrate significant sequence structural homology between proposed epitopes IgG1 ACPA fibrinogen. Two three homologous sequences were susceptible citrullination, this modification,...
The importance of cytotoxic T lymphocyte antigen-4 (CTLA-4) in immune regulation is unquestioned, yet a precise understanding which cells express it, and how it mediates inhibitory function, lacking. Regulatory are known to constitutively CTLA-4 intracellularly, whereas conventional require activation trigger expression. However comparative analysis trafficking regulatory subsets has not been performed.Here we assess expression antigen-specific responding immunizing antigen vivo analyse the...