A5091535438- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Reproductive System and Pregnancy
- Eosinophilic Esophagitis
- Immune cells in cancer
- CAR-T cell therapy research
- Adenosine and Purinergic Signaling
- Zebrafish Biomedical Research Applications
- SARS-CoV-2 and COVID-19 Research
- Hematopoietic Stem Cell Transplantation
- Transgenic Plants and Applications
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Nanoparticle-Based Drug Delivery
- Neonatal Respiratory Health Research
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- COVID-19 Clinical Research Studies
- Invertebrate Immune Response Mechanisms
University of Toronto
2014-2023
Canada Research Chairs
2019-2020
National Institutes of Health
1997-2019
Matsumoto Dental University
2019
Washington University in St. Louis
2019
Case Western Reserve University
2019
Sunnybrook Research Institute
2007-2018
Sunnybrook Health Science Centre
2008-2018
Sunnybrook Hospital
2014-2018
Centre for Social Innovation
2016-2017
The mouse CD8alpha+ DC subset excels at cross-presentation of antigen, which can elicit robust CTL responses. A receptor allowing specific antigen targeting to this and its equivalent in humans would therefore be useful for the induction antitumor CTLs. Here, we have characterized a C-type lectin NK cell group that named DC, receptor-1 (DNGR-1). DNGR-1 was found expressed mice high levels by CD8+ DCs low plasmacytoid but not other hematopoietic cells. Human also restricted expression small...
Infections with HIV, hepatitis B virus, and C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits function, thus promoting disease. Here we demonstrate natural killer (NK) cells have a negative impact on the development of immunity by using murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3 −/− , E4BP4 ) mice exhibited higher virus-specific response. In...
The NKR-P1 family of C-type lectin-like receptors are expressed on natural killer (NK) cells and NKT cells. We report the cloning characterization a cognate ligand for inhibitory mouse NK (NKR)-P1B NKR-P1D (CD161b/d). NKR-P1B/D is osteoclast lectin (Ocil), also known as Clr-b, member previously cloned group lectin-related (Clr) proteins linked to in gene complex (NKC). Expression Ocil/Clr-b tumor cell lines inhibits cell-mediated killing. Inhibition blocked with new mAb (4A6) specific...
The transcription factor E4bp4 (Nfil3) is essential for natural killer (NK) cell production. Here, we show that required at the NK lineage commitment point when progenitors develop from common lymphoid (CLPs) and must be expressed CLP stage differentiation toward to occur. To elucidate mechanism by which promotes development, identified a central core of factors can rescue production E4bp4−/− progenitors, suggesting they act downstream E4bp4. Among these were Eomes Id2, are later in...
To study molecular events involved in B lymphocyte development and V(D)J rearrangement, we have established an efficient system for the differentiation of embryonic stem (ES) cells into mature Ig-secreting lymphocytes. Here, show that lineage generated vitro from ES are functionally analogous to normal fetal liver-derived or bone marrow-derived at three important developmental stages: first, they respond Flt-3 ligand during early lymphopoietic progenitor stage; second, become targets Abelson...
Bipotent progenitors for T and natural killer (NK) lymphocytes are thought to exist among early precursor thymocytes. The identification functional properties of such a progenitor population remain undefined. We report the novel developmental stage during fetal thymic ontogeny that delineates T/NK-committed (NK1.1+/CD117+/CD44+/CD25−). Thymocytes at this in development phenotypically functionally distinguishable from pool multipotent lymphoid-restricted (B, T, NK) Exposure thymocytes or...
Abstract NK1.1 alloantigen expression can be used to define NK cells in certain mouse strains, such as B6 (NKR-P1C) and SJL (NKR-P1B). However, BALB/c do not react with the anti-NK1.1 mAb, PK136. To investigate NK1.1− phenotype of cells, we have undertaken epitope mapping genomic analysis Nkrp1 region. Bacterial artificial chromosome library reveals that, unlike Ly49 region, Nkrp1-Ocil/Clr region displays limited genetic divergence between mice. In fact, significant is confined Nkrp1b Nkrp1c...
Abstract Human peripheral blood NK cells may be divided into two main subsets: CD56 bright CD16 − and dim + . Since TGF‐β is known to influence the development of many leukocyte lineages, its effects on cell differentiation either from human CD34 Lin hematopoietic progenitor/stem in vitro or were investigated. represses progenitors inhibits cells. Moreover, also results conversion a minor fraction found cells, highlighting possible role former as developmental intermediate influencing...
Natural killer (NK) cells can recognize and kill tumor lacking "self" markers, such as class I MHC, but the basis for this recognition is not completely understood. NKR-P1 receptors are members of C-type lectin-related NK receptor superfamily that conserved from rodents to humans. Identification Clr ligands has facilitated functional analysis MHC-independent target cell by cells. One receptor-ligand pair, NKR-P1B:Clr-b, mediate "missing-self" infected cells, role axis in sensing stressed...
CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features fully convert into ILC1s. The molecular mechanisms governing such plasticity undefined. Here, we identified c-Maf as an essential regulator ILC3 homeostasis limits physiological ILC1 conversion. Phenotypic analysis status in Maf-deficient ILC3s, coupled with evaluation global changes transcriptome, chromatin accessibility,...
Abstract We recently described a population of fetal thymocytes with CD117+NK1.1+CD90lowCD25− phenotype, which were shown to contain committed T cell and NK progenitors. However, the characterization single restricted precursor potential was lacking. Here, using an in vitro model for differentiation, we provide conclusive evidence demonstrating existence clonal lineage-restricted progenitor. These results establish that phenotype represent bipotent
The mouse NK1.1 Ag originally defined as NK cell receptor (NKR)-P1C (CD161) mediates activation. Here, we show that another member of the CD161 family, NKR-P1B, represents a novel Ag. In contrast to NKR-P1C, which functions an activating receptor, NKR-P1B inhibits Association with Src homology 2-containing protein tyrosine phosphatase-1 provides molecular mechanism for this inhibition. existence these two Ags opposite suggests potential role NKR-P1 molecules, such those Ly-49 gene in...