A5101698017- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Protein Tyrosine Phosphatases
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Hematopoietic Stem Cell Transplantation
- Blood disorders and treatments
- Reproductive System and Pregnancy
- Cancer Cells and Metastasis
- Lymphoma Diagnosis and Treatment
- Diabetes and associated disorders
- Autoimmune and Inflammatory Disorders Research
- Complement system in diseases
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- Erythrocyte Function and Pathophysiology
- Cancer Mechanisms and Therapy
Montreal Clinical Research Institute
2015-2024
Rockefeller University
2018
University of California, San Francisco
2008
Molecular Oncology (United States)
2008
Weizmann Institute of Science
2000-2006
Blockade of the inhibitory checkpoint SIRPα-CD47 promotes phagocytosis cancer cells by macrophages and is a promising avenue in anti-cancer therapy. Productive strictly predicated on co-engagement pro-phagocytic receptors—namely, Fc receptors (FcRs), integrin CD11b, or SLAMF7—by their ligands cells. Here, we examine whether additional could be harnessed to broaden scope phagocytosis. Inflammatory stimuli, including multiple cytokines Toll-like receptor (TLR) ligands, augment efficiency fully...
CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 humans, that are present on antigen-presenting cells (APCs). However, both also expressed cells. By generating new knockout mouse strains lacking or the C57BL/6 background, we determined whereas was necessary for activation, ligand not required APCs. Rather, needed One exception during cytotoxicity, which Fluorescence resonance energy transfer (FRET) studies nonimmune provided evidence...
SAP (also named SH2D1A) is an intracellular adaptor molecule expressed in T cells, natural killer (NK) and some B cells. The gene mutated X-linked lymphoproliferative (XLP) disease, a human immunodeficiency characterized by faulty immune response to Epstein-Barr virus infection. Previous reports documented severe defects antibody production germinal center (GC) formation SAP-deficient humans mice genetically engineered lack expression. However, vitro studies adoptive transfer experiments...
Primary immunodeficiencies represent naturally occurring experimental models to decipher human immunobiology. We report a patient with combined immunodeficiency, marked by recurrent respiratory tract and DNA-based viral infections, hypogammaglobulinemia, panlymphopenia. He also developed moderate neutropenia but without prototypical pyogenic infections. Using whole-exome sequencing, we identified homozygous mutation in the inducible T cell costimulator ligand gene (ICOSLG; c.657C>G;...
The signaling lymphocytic activation molecule family of receptors has been implicated in the pathophysiology autoimmunity humans and mice. One member family, Ly108, was strongly linked to lupus susceptibility High expression a Ly108 isoform, Ly108-1, observed lymphocytes lupus-prone Herein, we examined molecular basis for influence on by studying signal transduction T cells. We that able mediate tyrosine phosphorylation implicating Vav-1, c-Cbl manner strictly dependent engagement...
The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) family of adapters includes SAP, Ewing's sarcoma-associated transcript-2 (EAT-2), and EAT-2-related transducer (ERT). These Src homology-2 (SH2) domain-only molecules play critical roles in immune regulation. prototype the SAP family, is mutated X-linked lymphoproliferative disease humans. Moreover, genetically engineered mice lacking one or more members have defects multiple cell types including T cells, natural...
Dendritic cells (DCs) capture and process antigens in peripheral tissues, migrate to lymphoid present the T cells. PTPN12, also known as PTP-PEST, is an intracellular protein tyrosine phosphatase (PTP) involved cell-cell cell-substratum interactions. Herein, we examined role of PTPN12 DCs, using a genetically engineered mouse lacking DCs. Our data indicated that was not necessary for DC differentiation, maturation, or cytokine production response inflammatory stimuli. However, it needed full...
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model not validated genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced activation responses in effector, but naive, cells. also have augmented cell-dependent autoimmunity and greater resistance anergy....
PTPN12 is a cytoplasmic protein tyrosine phosphatase (PTP) reported to be tumor suppressor in breast cancer, through its capacity dephosphorylate oncogenic receptor kinases (PTKs), such as ErbB2. However, the precise molecular and cellular impact of deficiency cancer progression remains fully clarified. Here, we addressed this issue by examining effect on vivo, mouse model ErbB2-dependent using conditional PTPN12-deficient mouse. Our studies showed that lack epithelial cells accelerated...
Signaling lymphocytic activation molecule (SLAM) family receptors (SFRs) can mediate either activating or inhibitory effects during natural killer cell (NK cell) activation. In this study, we addressed the global role, regulation, and mechanism of action SLAM in NK cells by analyzing a mouse lacking entire ∼400-kilobase Slam locus, which encodes all six SFRs CD48, ligand SFR 2B4. This displayed enhanced responses toward hematopoietic target cells. Analyses mice individual showed that...
Infection of mice by mouse cytomegalovirus (MCMV) triggers activation and expansion Ly49H+ natural killer (NK) cells, which are virus specific considered to be "adaptive" or "memory" NK cells. Here, we find that signaling lymphocytic molecule family receptors (SFRs), a group hematopoietic cell-restricted receptors, essential for the cells after MCMV infection. This activity is largely mediated CD48, an SFR broadly expressed on displaying augmented expression It also dependent CD48...
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral driven by a pool of neoplastic cells originating from T follicular helper (Tfh) and concomitant expansion B cells. Conventional chemotherapies for AITL have shown limited efficacy, as such, there need improved therapeutic options. Because originates Tfh cells, we hypothesized that tumors continue to rely on essential components intimate T-cell-B-cell (T-B) interactions. Using spontaneous mouse model (Roquinsan/+ mice),...
Abstract The encephalitogenic potential of oligodendrocyte-specific protein (OSP) in mice, its specific localization the intralamellar tight junctions CNS myelin, and detection autoreactivity against OSP multiple sclerosis (MS) strongly suggest relevance pathogenesis MS. In this study, we have characterized autoimmune T B cells that are associated with clinicopathological manifestations OSP-induced MS-like disease mice by using recombinant soluble mouse (smOSP) synthetic overlapping peptides...
Systemic administration of antigen/peptide for peripheral T cell tolerance has long been investigated as a potential approach to therapy autoimmune diseases. The multiple antimyelin reactivities likely be associated with sclerosis (MS) impose major difficulties in devising such an immune-specific therapeutic the disease, because targeting cells specific single autoantigen/epitope is unlikely sufficiently effective. Here, we present pilot study on possibility concomitantly inhibiting...
Expression of the signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) is critical for germinal center (GC) reaction and T cell–dependent antibody production. However, when SAP expressed normally, role associated SLAM family receptors (SFRs) in these processes nebulous. Herein, we established that presence SAP, SFRs suppressed expansion GC but facilitated generation antigen-specific B cells antibodies. favored antigen-reactive antibodies by boosting expression...