A5027364516- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Immune Response and Inflammation
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Atherosclerosis and Cardiovascular Diseases
- Virus-based gene therapy research
- Diabetes Management and Research
- Fatty Acid Research and Health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CRISPR and Genetic Engineering
- Inflammasome and immune disorders
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Immune responses and vaccinations
University of Toronto
2025
University College London
2017-2024
The Royal Free Hospital
2019-2020
Hôpital Maisonneuve-Rosemont
2017-2020
Centre for Immunity, Infection and Evolution
2017
CTLA-4 transendocytosis is elicited by self-antigens and down-regulates costimulatory ligands on migratory dendritic cells.
Significance Timely resolution of bacterial infections critically depends on phagocytosis invading pathogens by polymorphonuclear neutrophil granulocytes, followed apoptosis and removal macrophages. Neutrophils integrate cues from the inflammatory microenvironment. Here we show a Toll-like receptor 9-mediated mechanism, involving regulation phagocytosis-induced apoptosis, which DNA, pathogen-associated molecular pattern, danger signal mitochondrial DNA may impair host defense to bacteria...
Heterozygous mutations in CTLA-4 result an inborn error of immunity with autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications allogeneic hematopoietic stem transplantation. Here, we designed homology-directed repair (HDR) editing strategy that inserts cDNA into first intron genomic locus primary human cells. This resulted regulated expression CD4 + cells, functional studies demonstrated CD80 CD86...
Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), archetypal follicular helper T cell (Tfh) cytokine, shapes scale and polarization spontaneous chronic autoimmune as well transient immunization-induced GC. We find IL-21 receptor deficiency results smaller GC are profoundly skewed toward a light zone B phenotype plays key role selection cells for entry to dark zone. Light skewing previously mice lacking cycle...
Abstract Although IgA + long-lived plasma cells (LLPCs) generated following mucosal viral infection provide durable protection against reinfection, little is known about their generation. Here, we show that oral RV induces gut-resident LLPCs produce highly mutated protective IgA. Unlike RV-specific IgG LLPCs, were independently of MHCII expression by dendritic – rather B was both necessary and sufficient. cell also sufficient to induce a unique population T-bet follicular helper T (T FH 1)...
Abstract Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback this approach impaired regulatory homeostasis that requires signaling. Therefore, strategies restrict the effects blockade cells would be advantageous. Here we probe relative roles IL-2 maintaining Treg. We find provision counteracts loss induced by while minimally affecting conventional compartment. These...
Summary Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates response progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 advanced malignant melanoma before after treatment the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding blockade were characterised...
Curbing unwanted T cell responses by costimulation blockade has been a recognised immunosuppressive strategy for the last 15 years. However, our understanding of how best to deploy this intervention is still evolving. A key challenge heterogeneity in clinical response blockade, and an inability predict which individuals are likely benefit most. Here, we discuss recent findings based on use people with type 1 diabetes (T1D) place them context current literature. We profiling follicular helper...
Circulating follicular helper T cells (cTfh) can show phenotypic alterations in disease settings, including the context of tissue-damaging autoimmune or anti-viral responses. Using severe COVID-19 as a paradigm immune dysregulation, we have explored how cTfh phenotype relates to titre and quality antibody Severe was associated with higher titres neutralising S1 IgG evidence increased cell activation. ICOS, CD38 HLA-DR expressing correlated serum strength, interestingly expression TIGIT by...
Abstract Neutrophil dysfunction, resulting in delayed apoptosis and inefficient bacterial clearance, is a characteristic feature of severe pathologies, including sepsis cystic fibrosis. Human neutrophils detect respond to DNA (CpG DNA) through TLR9. We investigated the impact CpG on phagocytosis, phagocytosis-induced neutrophil clearance E coli. Culture human with (0.1–3.2 μg/ml) resulted decreased phagocytosis opsonized E. coli or yeast. upregulated C3R (CD11b) expression, downregulated...
Background: Heterozygous mutations in CTLA4 result an inborn error of immunity (IEI) (also known as primary immunodeficiency) with a severe clinical phenotype. Autologous T cell gene therapy may offer cure without the immunological complications allogeneic stem transplantation. The mutational landscape and requirement for tight regulation make viral addition approaches unappealing. Gene editing strategies permit alteration while retaining endogenous control machinery. Aims: We set out to...