A5026853110- Immune Cell Function and Interaction
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- CAR-T cell therapy research
- Cancer Mechanisms and Therapy
- Immune Response and Inflammation
- Corneal Surgery and Treatments
- Peptidase Inhibition and Analysis
- Macrophage Migration Inhibitory Factor
- NF-κB Signaling Pathways
- Monoclonal and Polyclonal Antibodies Research
- Ocular Diseases and Behçet’s Syndrome
- IL-33, ST2, and ILC Pathways
- Ocular Surface and Contact Lens
- Phagocytosis and Immune Regulation
- Corneal surgery and disorders
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Cytomegalovirus and herpesvirus research
- Allergic Rhinitis and Sensitization
- Signaling Pathways in Disease
- interferon and immune responses
Juntendo University
2014-2024
Guangzhou Medical University
2021
University Medical Center Utrecht
2013
Leiden University
2013
Tokyo Medical University
2012
Peter MacCallum Cancer Centre
2004-2011
The University of Melbourne
2011
Hy-Line (United States)
2008
Tokyo Medical and Dental University
2005-2006
University of California, San Francisco
2003-2004
Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in maintenance peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently identified as members B7 family but their expression at protein level remains largely unknown. To characterize B7-DC, we newly generated an anti-mouse mAb (MIH6) (TY25). MIH6 TY25 immunoprecipitated single molecule 43 42 kDa from lysate transfectants, respectively. Flow cytometric...
Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated this pathway development autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes prediabetic female nonobese diabetic (NOD) mice regardless age (from 1 10-wk-old), although it was most pronounced older mice. By contrast, cytotoxic...
Abstract Strategies to activate and rescue exhausted tumor-specific T cells, including the use of monoclonal antibodies (mAb) that block negative costimulatory receptors CTLA-4 PD-1 are proving very effective, but TIM3 has been relatively neglected as a target. Here we report an extensive characterization therapeutic activity mechanism action anti-mouse mAb against experimental carcinogen-induced tumors. For first time specifically define antitumor anti-TIM3 requiring IFN-γ producing CD8+...
Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) pathway plays a role in regulating peripheral tolerance murine EAE appears to be major contributor resistance of disease induction CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was progressive increase expression PD-1 its...
T cell Ig domain and mucin protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4+ effector differentiation. However, the function of TIM-1 on other populations unknown. Here, we show in vivo mice, predominantly expressed B rather than cells. Importantly, was large majority IL-10–expressing regulatory cells all major subpopulations, including transitional, marginal zone, follicular cells, as well population characterized CD1dhiCD5+. A low-affinity...
Abstract ICOS is a new member of the CD28 family costimulatory molecules that expressed on activated T cells. Its ligand B7RP-1 constitutively B Although blockade ICOS/B7RP-1 interaction inhibits cell-dependent Ab production and germinal center formation, mechanism remains unclear. We examined contribution to generation CXCR5+ follicular helper (TFH) cells in vivo, which preferentially migrate cell zone where they provide cognate help In spleen, anti-B7RP-1 mAb-treated or ICOS-deficient mice...
Microfold cells (M cells) are specialized epithelial situated over Peyer's patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL) is selectively expressed subepithelial stromal in PP domes. We found RANKL null mice have <2% wild-type levels M markedly diminished uptake 200 nm diameter fluorescent beads. Ab-mediated...
Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although mechanisms of SASP factor induction have been intensively studied, release mechanism and how factors influence tumorigenesis in biological context remain unclear. In this study, using mouse model obesity-induced hepatocellular carcinoma (HCC), we identified factors, which include interleukin-1β (IL-1β)- IL-1β-dependent IL-33, from hepatic stellate (HSCs) via gasdermin D (GSDMD)...
Abstract TNF-related apoptosis-inducing ligand (TRAIL), a new member of TNF family, induces apoptotic cell death various tumor cells. We recently showed that TRAIL mediates perforin- and Fas (FasL)-independent cytotoxic activity human CD4+ T clones. In the present study, we investigated expression function on murine lymphocytes by using newly generated anti-murine mAbs. Although freshly isolated T, B, or NK cells did not express detectable level their surface, remarkable was induced...
4-1BB (CDw137) and its ligand (4-1BBL) have been implicated in cellular immune responses. To further characterize the expression function of 4-1BBL, we newly generated an anti-mouse 4-1BBL mAb (TKS-1), which can inhibit interaction with 4-1BB. Flow cytometric analyses using TKS-1 indicated that was inducible on both CD4(+) CD8(+) splenic T cells by stimulation immobilized anti-CD3 mAb, but not expressed resting or activated cells. B anti-IgM antibody plus anti-CD40 peritoneal macrophages...
Asthma is caused by memory Th2 cells that often arise early in life and persist after repeated encounters with allergen. Although much known regarding how develop, there little information about the molecules regulate they have formed. Here we show costimulatory molecule OX40 expressed on CD4 cells. In already sensitized animals, blocking OX40-OX40L interactions at time of inhalation aerosolized antigen suppressed effector accumulation lung draining lymph nodes lung, prevented eosinophilia,...
CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and expressed on T, B, NK cells. The signal via plays pivotal roles in T-T T-B cell interactions. Here we demonstrate that overexpression activates NF-kappaB stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK). Deletion analysis cytoplasmic domain revealed C-terminal PIQEDYR motif was indispensable for both SAPK/JNK activation also required interaction with TNF receptor-associated (TRAF) 2 TRAF5, which have...
Infection of inbred mouse strains with Leishmania major is a well characterized model for analysis T helper (Th)1 and Th2 cell development in vivo. In this study, to address the role costimulatory molecules CD27, CD30, 4-1BB, OX40, which belong tumor necrosis factor receptor superfamily, Th1 cells vivo, we administered monoclonal antibody (mAb) against their ligands, CD70, CD30 ligand (L), 4-1BBL, OX40L, mice infected L. major. Whereas anti-CD70, anti-CD30L, anti–4-1BBL mAb exhibited no...
TNF-related apoptosis-inducing ligand (TRAIL) has been identified as a member of the TNF family that induces apoptosis in variety tumor cells, but its physiological functions are largely unknown. In present study, we examined expression and function TRAIL human CD4+ T cell clones by utilizing newly established anti-human mAbs. Human clones, HK12 4HM1, exhibited perforin-independent Fas (FasL)-independent cytotoxicity against certain target including lymphoma (Jurkat) keratinocyte (HaCaT)...
Because tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in cells and plays a critical role surveillance, its receptor is an attractive target for antibody-mediated therapy. Here we report that monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects TRAIL-sensitive vivo by recruiting Fc receptor–expressing innate immune cells, with no apparent systemic toxicity. Administration of agonistic anti-DR5...
Phagocytosis of apoptotic cells by myeloid has been implicated in the maintenance immune homeostasis. In this study, we found that T cell immunoglobulin- and mucin domain-containing molecule-4 (TIM-4) repressed tumor-specific immunity triggered chemotherapy-induced tumor death. TIM-4 was to be highly expressed on tumor-associated such as macrophages (TAMs) dendritic (TADCs) danger-associated molecular patterns (DAMPs) released from chemotherapy-damaged induced recruited bone marrow-derived...
TRAF5 [tumor necrosis factor (TNF) receptor-associated 5] is implicated in NF-κB and c-Jun NH 2 -terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, lymphotoxin-β receptor. To investigate functional role vivo , we generated TRAF5-deficient mice gene targeting. Activation either or tumor factor, CD40 was not abrogated traf5 −/− mice. However, B cells showed defects proliferation up-regulation various surface...
OX40 and its ligand (OX40L) have been implicated in T cell-dependent humoral immune responses. To further characterize the role of OX40/OX40L T-B cell interaction, we newly generated an anti-mouse OX40L mAb (RM134L) that can inhibit costimulatory activity transfectants for anti-CD3-stimulated proliferation. Flow cytometric analyses using RM134L indicated was inducible on splenic cells by stimulation with immobilized anti-CD3 a CD28-independent manner, while not expressed resting or activated...
Abstract A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 B7-DC interaction in development colitis. We first examined expression profiles PD-1 ligands both human inflammatory bowel disease murine...
OX40 ligand (OX40L) and (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family. Interaction OX40L with its is thought be important in T activation through cell/antigen-presenting interaction. However, involvement these pathogenesis rheumatoid arthritis (RA) remains unclear. To explore contribution OX40/OX40L interaction RA vivo, we evaluated effect neutralizing anti-OX40L monoclonal antibody (mAb) on development collagen-induced (CIA) DBA/1 mice as an animal...