A5088986458- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Allergic Rhinitis and Sensitization
- Mast cells and histamine
- Dermatology and Skin Diseases
- Food Allergy and Anaphylaxis Research
- Monoclonal and Polyclonal Antibodies Research
- IL-33, ST2, and ILC Pathways
- Cell Adhesion Molecules Research
- Antimicrobial Peptides and Activities
- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- CAR-T cell therapy research
- interferon and immune responses
- RNA Interference and Gene Delivery
- Pediatric health and respiratory diseases
- Eosinophilic Esophagitis
- Astrophysics and Cosmic Phenomena
- Viral Infections and Immunology Research
- Contact Dermatitis and Allergies
- Glycosylation and Glycoproteins Research
- Exercise and Physiological Responses
Juntendo University
2016-2025
Meiji University
1998-2024
Allergy Associates Research Center
2003-2022
Juntendo University Hospital
2006-2020
The University of Tokyo
1998-2018
Tokyo Medical University
1984-2015
Tokyo University of Science
1993-2011
University of Toronto
1998-2011
Stanford University
1975-2011
Jichi Medical University Saitama Medical Center
2011
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...
Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF processed to yield the soluble cytokine by metalloproteinases at cell surface of activated macrophages and T cells. In present study, we investigated whether FasL also released metalloproteinases. Treatment hydroxamic acid inhibitors matrix specifically led accumulation membrane-type (p40) on human cDNA transfectants cells, as estimated immunofluorescence...
An indefinite survival of cardiac allografts between fully incompatible mice strains was observed when monoclonal antibodies (MAbs) to intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) were simultaneously administered after the transplantation for 6 days. Mice with long-term surviving accepted skin grafts from donor-strain but rejected a third-party strain. Because MAbs ICAM-1 or LFA-1 alone insufficient prolonged tolerance, two probably acted...
IL-33, a member of the IL-1-related cytokines, is considered to be proallergic cytokine that especially involved in Th2-type immune responses. Moreover, like IL-1α, IL-33 has been suggested act as an “alarmin” amplifies responses during tissue injury. In contrast IL-1, however, precise roles those settings are poorly understood. Using IL-1- and IL-33-deficient mice, we found but not played substantial role induction T cell-mediated type IV hypersensitivity such contact delayed-type...
The natural killer T (NKT) cell ligand α-galactosylceramide (α-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12–mediated activities. Because of these similarities between the α-GalCer and IL-12, we investigated involvement IL-12 activation NKT cells by α-GalCer. We first established, using purified subsets various lymphocyte populations, selectively activates for production interferon (IFN)-γ. Production IFN-γ response to required produced dendritic...
B7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using GL-1 rat monoclonal antibody (mAb), we monitored expression of on mouse leukocytes with an emphasis dendritic cells. By cytofluorography, little or no was detected most types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, could be upregulated in culture. In case epidermal spleen cells, which become highly immunostimulatory cells during short period culture,...
Abstract Cytotoxic treatment with rabbit antiserum raised against purified glycosphingolipid “asialo GM1” was capable of eliminating natural killer (NK) activity spleen cells from different inbred mouse strains including CBA/J, C57BL/6, BALB/c, AKR, and athymic nude mice. The anti‐asialo GM 1 showed little cross‐reactivity structurally related glycolipids, e.g. 1, GD b asialo 2 in the microflocculation test. specific reactivity this NK confirmed by quantitative absorption anti‐NK graded...
NF-κB is activated by various stimuli including inflammatory cytokines and stresses. A key step in the activation of phosphorylation its inhibitors, IκBs, an IκB kinase (IKK) complex. Recently, two closely related kinases, designated IKKα IKKβ, have been identified to be components IKK complex that phosphorylate critical serine residues IκBs for degradation. previously NF-κB-inducing (NIK), which mediates TNFα IL-1, has demonstrated activate IKKα. Previous studies showed mitogen-activated...
Natural killer T (NKT) cells constitute a distinct subpopulation of with unique antigen specificity, prompt effector functions, and an unusual tissue distribution. NKT are especially abundant in the liver, but their physiological function this organ remains unclear. In present study, we examined possible contribution to murine model hepatitis induced by i.v. injection Con A. CD1-deficient mice lacking were highly resistant A-induced hepatitis. Adoptive transfer hepatic isolated from...
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to biological function NK cells has been unclear. Herein, we have demonstrated vivo induction mouse TRAIL expression on various tissue and correlated cell activation with TRAIL-mediated antimetastatic vivo. Expression was only constitutive a subset liver innate control Renca carcinoma hepatic metastases partially dependent....
Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge. To clarify functional of TLRs 4 mast cells, we examined bone marrow–derived cells (BMMCs) from TLR2 or gene-targeted mice. Peptidoglycan (PGN) Staphylococcus aureus stimulated a TLR2-dependent manner produce TNF-α, IL-4, IL-5, IL-6, IL-13, but not IL-1β. In contrast, LPS Escherichia coli TLR4-dependent IL-1β, IL-4 nor IL-5. Furthermore, TLR2- cell stimulation resulted...
Abstract Signals initiated through both the TCR complex and CD28 are required for optimal activation of T lymphocytes. Recently, it has been demonstrated that interacts with two different ligands, designated CD80 (B7/B7-1) CD86 (B70/B7-2). We have produced stable transfectants express CD80, CD86, or ligands examined their ability to costimulate cell proliferation, cytokine production, generation CTL. When we used small, resting human peripheral blood cells as responders, efficiently...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family type II membrane proteins, which constitutes one component T cell cytotoxicity. In this study, we investigated expression and function TRAIL in human peripheral blood (PBT) cells. Although freshly isolated PBT cells did not express detectable level on their surface, remarkable was rapidly induced surface both CD4+ CD8+ upon stimulation with anti-CD3 monoclonal antibody I...
Natural killer (NK) cells and interferon (IFN)-gamma have been implicated in immune surveillance against tumor development. Here we show that necrosis factor-related apoptosis-inducing ligand (TRAIL) plays a critical role the NK cell-mediated IFN-gamma-dependent surveillance. Administration of neutralizing monoclonal antibody TRAIL promoted development mice subcutaneously inoculated with chemical carcinogen methylcholanthrene (MCA). This protective effect was at least partly mediated by...
Intravenous injection of anti-asialo GM1, which has been shown to eliminate natural killer (NK) activity in vitro the presence complement, completely abolished NK against lymphoma cell line (YAC-1) spleen cells from athymic nude mice as well conventional mice. An immunofluorescence study revealed a decreased number asialo GM1 positive spleens injected with than those normal rabbit serum. In reduced activity, incidence tumor take and growth were enhanced when syngeneic (RL male-1), allogeneic...
The role of natural killer (NK) cells in the resistance mice to infections by several viruses was examined. Mice were specifically depleted NK i.v. injection rabbit antiserum asialo GM1, a neutral glycosphingolipid present at high concentrations on surface cells. Control left untreated or injected with normal serum. Four 6 hr later, these infected lymphocytic choriomeningitis virus (LCMV), mouse hepatitis (MHV), murine cytomegalovirus (MCMV), vaccinia virus. sacrificed 3 days post-infection...
Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge. To clarify functional of TLRs 4 mast cells, we examined bone marrow–derived cells (BMMCs) from TLR2 or gene-targeted mice. Peptidoglycan (PGN) Staphylococcus aureus stimulated a TLR2-dependent manner produce TNF-α, IL-4, IL-5, IL-6, IL-13, but not IL-1β. In contrast, LPS Escherichia coli TLR4-dependent IL-1β, IL-4 nor IL-5. Furthermore, TLR2- cell stimulation resulted...
Potent immunosuppressive drugs have significantly improved early patient survival after liver transplantation (LT). However, long‐term results remain unsatisfactory because of adverse events that are largely associated with lifelong immunosuppression. To solve this problem, different strategies been undertaken to induce operational tolerance, for example, maintenance normal graft function and histology without therapy, but achieved limited success. In pilot study, we aimed tolerance using a...
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER overload, resulting stress. To cope with stress, mammalian cells trigger a specific response known as protein (UPR). Although recent studies have indicated cross-talk between stress and oxidative mechanistic link is not fully understood. By using murine fibrosarcoma L929 cells, which tumor necrosis factor (TNF) α induces accumulation reactive oxygen species (ROS) cell death, we show that TNFα UPR ROS-dependent...
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...
Abstract The ability of BALB/c nude and C57BL/6 mice to eliminate tumor cells from the blood stream was severely impaired after a single inoculation 0.2 ml anti‐asialo BMI (asGMI) serum, diluted 1:40 1:320. number i.v.‐inoculated YAC‐I surviving in lungs pretreated with anti‐asGMI serum 28 times higher than control mice. In this respect, treated behaved similarly beige increase initial survival that induced by pre‐treatment resulted substantial artificial lung metastases developed. +/+ mice,...