A5007953730- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Mast cells and histamine
- Virus-based gene therapy research
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- Drug-Induced Hepatotoxicity and Protection
- Animal Genetics and Reproduction
- Allergic Rhinitis and Sensitization
- Reproductive System and Pregnancy
- Phagocytosis and Immune Regulation
- Peroxisome Proliferator-Activated Receptors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Toxoplasma gondii Research Studies
University of Tsukuba
2015-2025
Aichi Cancer Center
2024-2025
Nagoya University
2025
University of California, San Francisco
2014-2023
Parker Institute for Cancer Immunotherapy
2017-2023
Cancer Research Institute
2015
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
2015
Japan Science and Technology Agency
2011
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2011
Japan Society for the Promotion of Science
2007
NK cells provide important host defense against viruses and can differentiate into self-renewing memory after infection, alloantigen stimulation, cytokine stimulation. In this study, we investigated the role of IL-33 receptor ST2 in differentiation during mouse CMV (MCMV) infection. Although ST2-deficient (Il1rl1 (-/-)) Ly49H(+) develop normally MCMV naive Il1rl1 (-/-) exhibited profound defects MCMV-specific expansion, resulting impaired protection challenge. Additionally, enhanced m157...
Abstract Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK express Fc-gamma receptors (FcγRs) that engage the Fc region IgG. Studies investigating role FcγRs on mouse have been limited due to lack specific reagents. In this study, we characterize expression and biological consequences activating through their FcγRs. We demonstrate most CD16 receptor, a subset also expresses inhibitory CD32b receptor. Critically, these...
Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those WT splenocytes. Donor CD8 + T cells DNAM-1 showed less proliferation infiltration of the liver intestines recipient produced IFN-γ after coculture...
Group 1 innate lymphoid cells (G1-ILCs), including circulating natural killer (NK) and tissue-resident type ILCs (ILC1s), are immune sentinels critical for responses against infection cancer. In contrast to relatively uniform NK through the body, diverse ILC1 subsets have been characterized across within tissues in mice, but their developmental functional heterogeneity remain unsolved. Here, using multimodal vivo approaches fate-mapping targeting of interleukin 15 (IL-15)-producing...
Abstract Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ/δ (peroxisome proliferator-activated receptor β/δ) directly regulates CD300a in macrophages express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic inflammation with low numbers of lymph capillaries and dramatically expanded mesenteric nodes. As a result, these exhibit triglyceride malabsorption...
Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells are innate important for immediate host defence, they can differentiate into NK cells. The molecular mechanisms controlling this differentiation yet to be fully elucidated. Here we identify scaffold protein Themis2 as critical regulator cell and function. Themis2-deficient expressing Ly49H, an activating receptor mouse cytomegalovirus (MCMV) antigen m157, show enhanced augment protection...
DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B from a patient with Nasu-Hakola disease, recessive genetic disorder resulting loss of showed enhanced proliferation after stimulation anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) DAP12-associated immune receptor. Like cells, MAIR-II-deficient were...
Abstract NK cells play a critical role in host defense against viruses. In this study, we investigated the of NKG2D expansion after mouse CMV (MCMV) infection. Wild-type and NKG2D-deficient (Klrk1−/−) Ly49H+ proliferated robustly when infected with MCMV strains engineered to allow expression ligands, which enhanced response wild-type cells. Naive exclusively express NKG2D-L, pairs only DAP10, whereas NKG2D-S expressed by activated DAP10 DAP12, similar Ly49H. However, alone was unable drive...
Dendritic cells (DCs) genetically modified to express tumor-associated antigens (TAAs) would be promising tools in cancer immunotherapy. However, the use of retroviral vectors for such modifications is still a challenge because low transduction efficiency and gene silencing DCs. We have established an efficient method prepare DCs by vitro differentiation hematopoietic progenitor transduced with chicken ovalbumin (OVA) cDNA via gene-silencing-resistant vector GCDNsap packaged vesicular...
DNAX accessory molecule-1 (DNAM-1; CD226) is an activating immunoreceptor on T cells and NK cells. The interaction of DNAM-1 with its ligand CD155 expressed hematopoietic nonhematopoietic plays important role in innate adaptive immune responses. In this study, we investigated the DNAM-1-CD155 axis pathogenesis cell-mediated Con A-induced acute liver injury. Unexpectedly, DNAM-1-deficient (Cd226-/-) mice exhibited more severe injury higher concentrations IL-6 TNF-α than did wild-type (WT)...
NK cells are cytotoxic innate lymphocytes that play a critical role in antitumor immunity. recognize target by using repertoire of activating receptors and exert the effector functions. Although magnitude activation signals through controls cell function, it has not been fully understood how these modulated cells. In this study, we found scaffold protein, THEMIS2, inhibits receptor signaling. Overexpression THEMIS2 attenuated function human cells, whereas knockdown enhanced it....
Abstract Acute liver injury is a life‐threatening disease. Although immune responses are involved in the development and exacerbation of acute injury, cellular molecular mechanisms not fully understood. Intravenous administration plant lectin concanavalin A (ConA) widely used as model injury. ConA triggers T cell activation cytokine production by crosslinking glycoproteins, including receptor, leading to infiltration myeloid cells into subsequent amplification inflammation liver. Thus,...
Abstract: We have demonstrated that dendritic cells (DCs) genetically modified to express tumor‐associated antigens (TAAs) with retroviral vectors elicit more potential anti‐tumor effect than those loaded peptides because they can prime antigen‐specific CD4+ T resulting in production of tumor‐specific antibody. In this study, we showed the importance antigen presentation via a major histocompatibility complex (MHC) class II molecule cancer immunity against non‐membrane bound TAAs such as...
Abstract Natural killer cells are critical in the immune response to infection and malignancy. Prior studies have demonstrated that Crk family proteins can influence cell apoptosis, proliferation, transformation. In this study, we investigated role of mouse NK differentiation host defense using a CMV model. The number cells, maturational state, majority NKR repertoire was similar x Crk-like (CrkL)–double-deficient wild type cells. However, were required for optimal activation, IFN-γ...
Silencing of transduced genes hampers production transgenic mice using retroviral vectors. We show stable expression the enhanced green fluorescent protein (EGFP) gene in chimeric generated from retrovirally embryonic stem cells. The vector was a murine cell virus-typed (GCDsap) which long terminal repeat and primer-binding site were derived PCC4 cell-passaged myeloproliferative sarcoma virus endogenous retrovirus dl587rev, respectively. To increase viral titer, packaged with vesicular...
Abstract Group 1 innate lymphoid cells (G1-ILCs), including circulating natural killer (NK) and tissue-resident type ILCs (ILC1s), are immune sentinels critical for responses against infection cancer. In contrast to relatively uniform NK through the body, diverse ILC1 subsets have been characterized across within tissues in mice, but their developmental functional heterogeneity remain unsolved. Here, using multimodal vivo approaches fate-mapping targeting of interleukin 15 (IL-15)-producing...
We appreciate the comments of Seth et al. (1), because they provide an important finding that is supplementary to our paper (2). They show recipient mice deficient in CD155 (Cd155−/− mice), a ligand for DNAM-1 (DNAX accessory molecule-1, CD226), exhibited shorter rather than longer survival WT after bone marrow transplantation (BMT) with full MHC disparity. also donor CD4+, but not CD8+, T cells were responsible poor Cd155−/− mice, suggesting interaction on organs receptor CD4+ protects from...