A5025143550- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- T-cell and Retrovirus Studies
- Mast cells and histamine
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Veterinary Oncology Research
- Acute Myeloid Leukemia Research
- Animal Virus Infections Studies
- Immunodeficiency and Autoimmune Disorders
- Neonatal Respiratory Health Research
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Renal and related cancers
- Cancer-related Molecular Pathways
- NF-κB Signaling Pathways
- Hematopoietic Stem Cell Transplantation
- Hedgehog Signaling Pathway Studies
- Asthma and respiratory diseases
- Developmental Biology and Gene Regulation
- Chronic Myeloid Leukemia Treatments
- Platelet Disorders and Treatments
Tokyo University of Science
2012-2024
Institute of Aging
2017
Institute for Biological Sciences
2008-2011
Tokyo Medical and Dental University
2006
Keio University
2006
University of California, San Francisco
2006
The University of Tokyo
1989-2001
Japan Science and Technology Agency
2001
Molecular Biology Consortium
2001
Tokyo University of Agriculture
1989-1997
The aggregation of high affinity IgE receptors (Fcε receptor I [FcεRI]) on mast cells is potent stimulus for the release inflammatory and allergic mediators from cytoplasmic granules. However, molecular mechanism degranulation has not yet been established. It still unclear how FcεRI-mediated signal transduction ultimately regulates reorganization cytoskeleton these events lead to degranulation. Here, we show that FcεRI stimulation triggers formation microtubules in a manner independent...
Notch receptors play various roles for cell fate decisions in developing organs, although their functions at the level are poorly understood. Recently, we found that Notch1 and its ligand each expressed juxtaposed compartments follicles of bursa Fabricius, central organ chicken B development. To examine function cells, a constitutively active form was line, DT40, by Cre/<i>loxP</i>-mediated inducible expression system. Remarkably, caused growth suppression accompanied cycle inhibition...
B cell antigen receptor signals development, activation, proliferation, or apoptosis of cells depending on their condition, and its proper signaling is critical for activation homeostasis the immune system. The cell-restricted adaptor protein BASH (also termed BLNK/SLP-65) rapidly phosphorylated by tyrosine kinase Syk after BCR ligation binds to various proteins. structurally resembles SLP-76, which essential T development signaling. To evaluate role in function vivo , we disrupted alleles...
Mucosal epithelial M cells provide an efficient portal of entry for microorganisms. Initially defined by their irregular microvilli and abundant transcytotic channels in the avian bursa Fabricius, also are found lymphoid follicle-associated epithelium mammalian appendix, Peyer's patches, other mucosal surface-lymphoid interfaces. We describe here a previously unrecognized cathelicidin gene chickens, chCATH-B1, that is expressed exclusively Fabricius. Like mature peptides identified...
Cerebellar granule cell precursors (GCPs) and cells (GCs) represent good models to study neuronal development. Here, we report that the transcription factor myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in regulation of mouse GC We found Meis1 is expressed lineage astrocytes cerebellum during Targeted disruption gene specifically resulted smaller cerebella with disorganized lobules. Knock-down/knock-out (KO) experiments for vitro assays showed binds an upstream...
Abstract The bursa of Fabricius is a gut-associated lymphoid organ that essential for the generation diversified B cell repertoire in chicken. We describe here novel gene preferentially expressed bursal cells. encodes an 85-kDa protein, designated BASH (B adaptor containing SH2 domain), contains N-terminal acidic domains with domain-binding phosphotyrosine-based motifs, proline-rich domain, and C-terminal domain. shows substantial sequence similarity to SLP-76, protein functioning TCR-signal...
Abstract Myeloma is one of the interleukin (IL)‐6‐related diseases to which abnormal expression IL‐6 has been reported be linked. We examined in vivo inhibitory effect anti‐human receptor (IL‐6R) antibody on human myeloma cell growth mice. SCID mice were subcutaneously inoculated with solid tumor line S6B45 was acting as an autocrine factor. Ten intraperitoneal administrations 100 μg IL‐6R PM1 at 48‐h intervals strongly inhibited cells when administration started 24 h after inoculation. The...
Hematopoietic stem cells in the bone marrow have capacity to both self-renew and generate all of hematopoietic system. The balance these two activities is controlled by cell-intrinsic regulatory mechanisms as well extrinsic signals from microenvironment. Here we demonstrate that Meis1, a TALE family homeodomain transcription factor involved numerous embryonic developmental processes, selectively expressed stem/progenitor cells. Conditional Meis1 knockout adult resulted significant reduction...
Abstract Extramedullary hematopoiesis (EMH) in postnatal life is a pathological process which the differentiation of hematopoietic stem/progenitor cells (HSPCs) occurs outside bone marrow (BM) to respond emergencies. The spleen major site for EMH; however, cellular and molecular nature stromal cell components supporting HSPC maintenance, niche EMH remain poorly understood compared growing understanding BM at steady-state as well emergency hematopoiesis. In present study, we demonstrate that...
A minor population of M cells within the follicle-associated epithelium (FAE) intestinal Peyer's patches (PPs) serves as a major portal for entry exogenous antigens. Characterization mammalian cells, including identification M-cell surface molecules used bacterial uptake, has been hampered by their relative rarity. In contrast, constitute virtually all FAE in avian bursa Fabricius. We therefore performed comparative gene expression profiling chicken and murine to identify commonly expressed...
Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine receptor (S1P(1)) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis internalization. Furthermore, differing from previously reported S1P(1) antagonists, TASP0277308 demonstrated...
The TALE-class homeoprotein MEIS1 specifically collaborates with HOXA9 to drive myeloid leukemogenesis. Although alone has only a moderate effect on cell proliferation in vitro, it is essential for the development of HOXA9-induced leukemia vivo. Here, using murine models leukemogenesis, we have shown that promotes leukemic homing and engraftment bone marrow enhances cell-cell interactions cytokine-mediated migration. We analyzed global DNA binding cells as well gene expression alterations...
Tumor necrosis factor alpha (TNF-alpha) induced morphologic changes such as chromatin condensation and cell shrinkage in a feline fibroblastic line (CRFK) chronically infected with immunodeficiency virus (FIV) but not uninfected CRFK cells. DNA extracted from TNF-alpha-treated cells FIV showed ladder of nucleosomal DNA, indicating that this cytocidal effect by TNF-alpha was due to programmed death, or apoptosis. These findings may have implications for understanding the pathogenesis...
Abstract G protein–coupled receptors (GPCRs) regulate many cellular processes in response to various stimuli, including light, hormones, neurotransmitters, and odorants, some of which play critical roles innate adaptive immune responses. However, the physiological functions GPCRs involvement them autoimmune diseases central nervous system remain unclear. Here, we demonstrate that GPR141, an orphan GPCR belonging class A receptor family, suppresses High GPR141 messenger RNA levels were...
The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for antigen receptor (BCR)-mediated activation, proliferation, and differentiation of cells. BCR-mediated tyrosine-phosphorylation BASH creates binding sites signaling effectors such as phospholipase Cγ (PLCγ)2 Vav, while the function its COOH-terminal unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, protein that inducibly...
Abstract Involvement of IL-6 in the development vasculitis and polyclonal gammopathy feline infectious peritonitis (FIP) was investigated, by using proliferative responses two IL-6-dependent murine hybridoma cell clones, B3B1 MH60.BSF-2 cells. A significant activity found sera ascitic fluids cats with FIP, whereas no detected from healthy cats. In these FIP cats, significantly higher than that sera. Peritoneal exudate cells were also to release a high level culture supernatant. The eluted...
Cross-linking of the high-affinity IgE receptor (FcϵRI) on mast cells by IgE–antigen complex triggers signal transduction cascades leading to release inflammatory mediators and production cytokines, which are critical for development allergic reactions. We have identified a novel member BASH/SLP-76 immunoreceptor-coupled adaptor family expressed in cells, termed MIST (for cell immunoreceptor transducer), has later been found be identical recently reported cytokine-dependent hemopoietic...
Abstract Constitutive expression of suppressors cytokine signaling (SOCS)1 in T lineage vivo attenuated and resulted a dramatic reduction the number naive CD44lowCD62Lhigh CD4 cells spleen. After adoptive transfer thymocytes from SOCS1 transgenic mice into normal recipients, rapidly disappeared spleen within 1 wk. Likewise, cell-specific deletion STAT5a/b similar phenotype characterized by loss cells. Thus, STAT5-mediated is crucial for promoting cell survival. However, forced constitutively...