A5103011051- interferon and immune responses
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Cytokine Signaling Pathways and Interactions
- Neuroendocrine Tumor Research Advances
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IgG4-Related and Inflammatory Diseases
- Virology and Viral Diseases
- Oral and Maxillofacial Pathology
- Hepatitis B Virus Studies
- Nuclear Receptors and Signaling
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- RNA regulation and disease
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Hepatitis C virus research
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
- Asthma and respiratory diseases
- Cancer-related molecular mechanisms research
- Cardiac Valve Diseases and Treatments
- Cancer Research and Treatments
Sapporo Medical University
2017-2024
Hokkaido University
2010-2023
Aomori University
2019
Kyushu University
2004-2011
St. Petersburg Institute of Bioregulation and Gerontology
2005
Institute of Biomedical Science
2004
Fukushima Medical University
2001-2003
Kurume University
1964-1994
Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator signal transducer and activator transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels SOCS3 in T cells result type 2 helper cell (Th2) skewing lead to hypersensitivity allergic diseases. To define the physiological roles cells, we generated cell–specific conditional knockout mice. We found mice lacking showed reduced immune responses not only ovalbumin-induced airway...
Approximately 20% of human cancers are estimated to develop from chronic inflammation. Recently, the NF-κB pathway was shown play an essential role in promoting inflammation-associated cancer, but JAK/STAT pathway, another important signaling proinflammatory cytokines, remains be investigated. Suppressor cytokine signaling-1 (SOCS1) acts as physiological regulator responses, and silencing SOCS1 gene by DNA methylation has been found several cancers. Here, we demonstrated that SOCS1-deficient...
It has been shown that transforming growth factor β1 (TGF-β1) is critical in the generation of CD4+CD25+Foxp3+-inducible regulatory T cells (iTregs) from naïve CD4+T cells. However, contrast to natural Tregs, TGF-β1-induced iTregs rapidly lose both Foxp3 expression and suppression activity. We found levels were maintained by addition anti-interleukin 4 (IL-4) antibody or STAT6 gene deletion. Thus, IL-4 an important suppressor induction, helper 2 development a major cause for disappearance...
Abstract Double-stranded RNA directly acts on fibroblast and myeloid lineages to induce necroptosis as in TNFα. Here, we investigated whether this type of cell death occurred cancer cells response polyinosinic–polycytidylic acid (polyI:C) the pan-caspase inhibitor z-Val-Ala-Asp fluromethyl ketone (zVAD). We found that colon line CT26 is highly susceptible necroptosis, revealed by staining with annexin V/propidium iodide. possess sensors, TLR3 MDA5, which are upregulated interferon...
IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory characterized by elevation of serum IgG4 level as well infiltration IgG4+ plasma cells in various affected organs. The etiology IgG4-RD still not fully understood. Since more prevalent the elderly, aging itself considered to be an important risk factor IgG4-RD. However, relationship between pathogenesis and immunosenescence remains unknown. To clarify age-related features underlying IgG4-RD, we focused on T follicular regulatory...
Abstract Basal forebrain cholinergic neurons (BFCNs) are involved in cognitive functions such as learning and memory, affected several neurodegenerative diseases (e.g. Alzheimer's disease). Despite their importance, the molecular mechanisms of development not fully elucidated. A recent report demonstrated that some BFCNs adult rat positive for L3/Lhx8, a LIM homeobox transcription factor. To examine function L3/Lhx8 BFCNs, we generated gene‐disrupted mice. In these mice, cells expressing...
The engagement of Toll-like receptor 3 (TLR3) leads to the oligomerization adaptor TICAM-1 (TRIF), which can induces either three acute cellular responses, namely, cell survival coupled Type I interferon production, or death, via apoptosis necrosis. specific response elicited by TLR3 determines fate affected cells, although switching mechanism between two death pathways in TLR3-stimulated cells remains molecularly unknown. Tumor necrosis factor α (TNFα)-mediated proceed a non-apoptotic...
Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays critical...
Abstract Syndecan‐1, ‐2, ‐3, and ‐4 are heparan sulfate proteoglycans that differentially expressed during development wound repair. To determine whether syndecans also involved in brain injury, we examined the expression of syndecan core proteins genes cryo‐injured mouse brain, using situ hybridization. All mRNA transcripts were similarly region surrounding necrotic tissue, exhibiting peak levels at day 7 after injury. Comparison with cellular markers showed reactive astrocytes primary...
Lipopolysaccharide (LPS) activates macrophages through toll-like receptor (TLR) 4. Although the mechanism of TLR signaling pathway has been well documented, negative regulation in response to LPS, particularly LPS tolerance, is still poorly understood. In this study we identified and characterized a novel interferon- LPS-inducible gene, FLN29, which contains TRAF6-related zinc finger motif TRAF family member-associated NF-κB activator-related sequences. The induction FLN29 was dependent on...
TGF-beta1 is a well-known immunosuppressive cytokine; however, little known of the effect on antigen-presenting cells (APCs). In this report, we investigated molecular mechanisms suppressive effects APCs including dendritic and macrophages. Although did not greatly affect activation APCs, as assessed by induction IL-12 or upregulation CD40 in response to LPS, it strongly inhibited IFN-gamma-induced nitric oxide (NO) production from macrophages cells. Using murine macrophage-like cell line...
The aim was to study the pathological role of lymphocytes with a peripheral T helper-cell-like phenotype (PD-1+CXCR5−CD4+) in IgG4-related disease (IgG4-RD). PD-1+CXCR5−CD4+ cells blood patients IgG4-RD (n = 53), SS 16) and healthy volunteers 34) as controls were analysed by flow cytometry. Correlations between results obtained cytometry clinical parameters relevant also analysed. percentage absolute number PD-1+CXCR5− within total CD4+ significantly increased compared those volunteers....
Hepatitis B virus (HBV) barely induces host interferon (IFN)-stimulated genes (ISGs), which allows efficient HBV replication in the immortalized mouse hepatocytes as per human hepatocytes. Here we found that transfection of Isg20 plasmid robustly inhibits HBV-infected irrespective IRF3 or IFN promoter activation. Transfection is thus effective to eradicate infected genome ε-stem pgRNA (active moiety) failed induce hepatocytes, while control polyI:C (a viral dsRNA analogue mimic) activated...
Abstract The glutamatergic dysfunction has been implicated in pathophysiology of schizophrenia. Group III metabotropic glutamate receptor 4 (mGluR4), 6, 7, and 8 are thought to modulate transmission the brain by inhibiting release at synapse. We tested association schizophrenia with GRM8 using 22 single nucleofide polymorphisms (SNPs) average intervals 40.3 kb region 100 case‐control pairs for SNPs. Although we observed significant associations two SNPs, SNP18 (rs2237748, allele: P = 0.0279;...
Objectives: The aim of this study was to determine pathological features T peripheral helper (Tph)-like (PD-1+CXCR5−CD4+ T) cells in IgG4-related disease (IgG4-RD).Methods: Tph-like the...
Caveolin‐1 (Cav‐1) has been suggested to function as a negative regulator of mitogen‐stimulated proliferation and the Ras‐p42/44 ERK (MAP kinase) pathway in variety cell types. However, molecular basis this suppression not clarified. Spred/Sprouty family proteins are also regulators by interacting with Raf‐1. The contain cysteine‐rich (CR) domain at C‐terminus, which is thought be palmitoylated like Cav‐1 necessary for membrane anchoring. In study, we demonstrated that Spred‐1 localized...
L-Ergothioneine (EGT) is a naturally-occurring amino acid which characterized by its antioxidant property; yet, the physiological role of EGT has yet to be established. We investigated immune-enhancing properties EGT, and found that it acts as potentiator toll-like receptor (TLR) signaling. When mouse bone marrow-derived macrophages (BMDMs) were pretreated with TLR signal-mediated cytokine production was augmented in BMDMs. The results reproducible TLR2, 3, 4 7 agonists. In particular, IL-6...
ABSTRACT Viral RNA represents a pattern molecule that can be recognized by sensors in innate immunity. Humans and mice possess cytoplasmic DNA/RNA for detecting viral replication. There are number of DEAD (Asp‐Glu‐Ala‐Asp; DExD/H) box‐type helicases mammals, among which retinoic acid‐inducible gene 1 (RIG‐I) melanoma differentiation‐associated protein 5 (MDA50) indispensable sensing; however, they functionally supported directly bind or replicative intermediates to convey signals RIG‐I MDA5....