A5026278298- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- NF-κB Signaling Pathways
- DNA Repair Mechanisms
- Systemic Lupus Erythematosus Research
- DNA and Nucleic Acid Chemistry
- Immune cells in cancer
- RNA Research and Splicing
- Allergic Rhinitis and Sensitization
- Cell Adhesion Molecules Research
- Biochemical Analysis and Sensing Techniques
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- Planarian Biology and Electrostimulation
- Lymphatic System and Diseases
- RNA and protein synthesis mechanisms
- Veterinary Oncology Research
- Cancer-related gene regulation
- Phagocytosis and Immune Regulation
- Protein Tyrosine Phosphatases
- Peroxisome Proliferator-Activated Receptors
Tokyo Medical University
2022-2025
Niigata University
2015-2022
Tokyo Medical and Dental University
2022
RIKEN Center for Integrative Medical Sciences
2004-2017
Toxicologie, Pharmacologie et Signalisation Cellulaire
2013
Chiba University
2001-2007
University Health Network
2006
University of Toronto
2006
Tokyo University of Science
1998-2005
Chiba Cancer Center
2005
Naive T cells differentiate into various effector cells, including CD4+ helper cell subsets and CD8+ cytotoxic (CTL). Although (CD4+CTL) also develop from naive the mechanism of development is elusive. We found that a small fraction express class I–restricted cell–associated molecule (CRTAM) upon activation possesses characteristics both cells. CRTAM+ secrete IFN-γ, CTL-related genes, such as eomesodermin (Eomes), Granzyme B, perforin, after cultivation, exhibit function, suggesting are...
The transcriptional repressor BTB and CNC homology 2 (Bach2) is thought to be mainly expressed in B cells with specific functions such as class switch recombination somatic hypermutation, but its function T not known. We found equal Bach2 expression analyzed using Bach2-deficient (-/-) mice. Although T-cell development was normal, numbers of peripheral naive were decreased, which rapidly produced Th2 cytokines after TCR stimulation. Bach2(-/-) highly genes related effector-memory CCR4, ST-2...
Abstract Ag recognition by T lymphocytes induces immune synapse formation and recruitment of signaling molecules into a lipid raft. Cbp/PAG is Csk-associated membrane adapter protein exclusively localized in We identified NHERF/EBP50 as Cbp-binding molecule, which connects the raft cytoskeleton binding to both Cbp through its PDZ domain ezrin-radixin-moesin C terminus. Overexpression reduced mobility on cell surface unstimulated cells prevented subsequent activation, whereas mutant incapable...
AP-3 is a member of the adaptor protein (AP) complex family that regulates vesicular transport cargo proteins in secretory and endocytic pathways. There are two isoforms AP-3: ubiquitously expressed AP-3A neuron-specific AP-3B. Although physiological role has recently been elucidated, AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, subunit μ3B−/− suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses these mice....
Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity multiple DNA polymerases required to ultimately introduce mutations. polymerase η (Polη) has been implicated in mutations at A/T, but involved C/G have not identified. We generated mutant mice expressing (Polθ) specifically devoid activity. Compared with WT mice, Polq-inactive (Polq, gene encoding Polθ) exhibited a reduced level serum IgM and IgG1. The mounted...
IRAK-4 is a protein kinase that pivotal in mediating signals for innate immune responses. Here, we report signaling also essential eliciting adaptive Thus, the absence of IRAK-4, vivo T cell responses were significantly impaired. Upon receptor stimulation, recruited to lipid rafts, where it induces downstream signals, including C activation through association with Zap70. This pathway was found be required optimal nuclear factor kappaB. Our findings suggest cells use this critical regulator...
A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By this strategy, activating molecule 1 (NFAM1) cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing surface belonging the Ig superfamily is predominantly expressed in spleen B cells. NFAM1 crosslinking induced ITAM phosphorylation, ZAP-70/Syk...
In vivo immune response is triggered in the lymph node, where lymphocytes for entry into, retention at, and migration to effector sites are dynamically regulated. The molecular mechanism underlying regulation key elucidating of response. this study, we describe function adhesion molecule class I-restricted T cell-associated (CRTAM) regulating CD8+ cell within node eventually function. We previously identified CRTAM as a receptor predominantly expressed on activated cells, nectin-like...
To maintain various T cell responses and immune equilibrium, activation signals triggered by antigen receptor (TCR) must be regulated inhibitory signals. Gab2, an adaptor protein of the insulin substrate-1 family, has been shown to involved in downstream signaling from cytokine receptors. We investigated functional role Gab2 TCR-mediated signal transduction. was phosphorylated ZAP-70 co-precipitated with phosphoproteins, such as ZAP-70, LAT, CD3zeta, upon TCR stimulation. Overexpression...
NK cells and CD8+ T exhibit cytotoxicity cytokine production upon recognizing target through cell–cell interaction. We screened the molecules involved in recognition regulation of these using cDNA subtraction between naive activated cells. identified class I-restricted cell-associated molecule (CRTAM), a two Ig domain-bearing surface receptor, as rapidly transiently expressed on activation. CRTAM is dimer cell surface, its expression transcriptionally regulated. Using an expression-cloning...
Abstract Activating NK cell receptors transduce signals through ITAM-containing adaptors, including FcRγ and DAP12. Although the caspase recruitment domain (CARD)9-Bcl10 complex is essential for FcRγ/DAP12-mediated NF-κB activation in myeloid cells, its involvement receptor signaling unknown. Herein we show that deficiency of CARMA1 or Bcl10, but not CARD9, resulted severe impairment cytokine/chemokine production mediated by activating due to a selective defect activation, whereas...
Blockade of immune checkpoint receptors has shown outstanding efficacy for tumor immunotherapy. Promising treatment with anti-lymphocyte-activation gene-3 (LAG-3) already been recognized as the next efficacious treatment, but there is still limited understanding mechanism LAG-3-mediated suppression. Here, utilizing high-resolution molecular imaging, we find a CD4 T cell suppression via LAG-3, in which LAG-3-bound major histocompatibility complex (MHC) class II molecules on antigen-presenting...
<title>Abstract</title> Various improvements have been made to chimeric antigen receptor (CAR)-T cells enhance their antitumor effects and expand indications various cancer types. Although second-generation CARs directly induce second signals in a linear pathway via own costimulatory domain such as CD28, CAR-T themselves express receptors, which additional parallel. To clarify the differences between these two types of signals, we analyzed CD28-mediated signalosomes using high-resolution...
The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, intricate details structures and associated FSC subsets are not fully understood. Using gene reporter mice, we sought to discover unrecognized FSCs LN. four previously identified cortex clearly distinguished expression pattern reporters including PDGFR, CCL21-ser,...
Abstract The pre-TCRα (pTα) is exclusively expressed in immature thymocytes and constitutes the pre-TCR complex with TCRβ, which regulates early T cell differentiation. Despite recent identification of pTα enhancer, contribution promoter region, direct DNA-protein interaction, regulation such interaction along development have not been investigated. We analyzed region identified critical elements for transcription gene. was found to contain two consecutive E-box that are transcription....
SUMMARY The effect of immunosuppression on Mycoplasma hyopneumoniae infection was evaluated by comparing data from infected, thymectomized, and antithymocyte serum-treated pigs (group 1) with infected 2) noninfected 3) healthy pigs. After groups 1 2 were inoculated intranasally M hyopneumoniae, mycoplasmas tended to multiply slightly more in the lungs bronchial lymph nodes group than that Organisms also isolated spleen 3 Pneumonia developed characterized massive peribronchial,...
Type-2 bitter taste receptors (Tas2Rs) are a large family of G protein-coupled that expressed in the oral cavity and serve to detect substances with tastes foods medicines. Recent evidence suggests Tas2Rs also extraorally, including immune cells. However, role cells remains controversial. Here, we demonstrate Tas2R126, Tas2R135, Tas2R143 mouse neutrophils, but not other such as macrophages or T B lymphocytes. Treatment bone marrow-derived neutrophils from wild-type mice Tas2R126/143 agonists...
With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into consideration, but without a method to evaluate them. Here we establish an advanced imaging system visualize human PD-1 microclusters, which minimal T cell receptor (TCR) signaling unit co-localizes with inhibitory co-receptor vitro. In these...
In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The function of LNs involves resident macrophages tightly associated with unique sinus structures. Moreover, an intermittently arranged LN pathway is considered to cooperatively prevent substances from entering blood circulation. However, functional significance tissue microarchitecture, cellular composition, individual "LN chain" system not fully understood. To explore...
Organized tissue structure in the secondary lymphoid organs (SLOs) tightly depends on development of fibroblastic stromal cells (FSCs) mesenchymal origin; however, mechanisms this relationship are poorly understood. In study, we specifically inactivated canonical NF-κB pathway FSCs vivo by conditionally inducing IκBα mutant a Ccl19-IκBSR mouse system which activity is likely to be suppressed fetal FSC progenitors. Given that activation essential for SLO development, animals were expected...