A5077901251- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Psoriasis: Treatment and Pathogenesis
- Pancreatic function and diabetes
- Thyroid Disorders and Treatments
- Diabetes and associated disorders
- Cell Adhesion Molecules Research
- Stress Responses and Cortisol
- Asthma and respiratory diseases
- Signaling Pathways in Disease
- Genetics, Aging, and Longevity in Model Organisms
- Cancer, Lipids, and Metabolism
- Erythrocyte Function and Pathophysiology
- CAR-T cell therapy research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Immune responses and vaccinations
- Trace Elements in Health
- Immunodeficiency and Autoimmune Disorders
- Vagus Nerve Stimulation Research
- Neonatal Respiratory Health Research
- RNA regulation and disease
Hyogo University
2022-2024
Hyogo Medical University
2019
Hokkaido University
1998-2018
Osaka University
2007-2018
Osaka International University
2015-2018
Yale University
2015-2018
Ube Frontier University
2011-2015
Japan Science and Technology Agency
2008-2015
Keio University
2009
The University of Tokyo
1989-1994
IL-17-producing Th (Th17) comprise a distinct lineage of pro-inflammatory that are major contributors to autoimmune diseases. Treatment with IL-6 and transforming growth factor β (TGFβ) induces naive CD4+ T cells generate Th17, which also requires expression the IL-6/TGFβ target RORγt. We reported transduces two signaling pathways via tyrosine redidues signal transducer gp130: one depends on transducers activators transcription (STAT)-3 activation other Src homology region 2...
Significance Zinc deficiency is known to trigger lymphopenia, but the mechanisms behind zinc-mediated lymphocyte maintenance have been unclear. We demonstrated that zinc uptake into cells through transporter ZIP10 essential for cell survival in early B-cell development. The ablation of caused an increase caspase activity accompanied by reduced intracellular developmental stages. JAK-STAT pathways regulated expression, and expression was correlated with STAT activation lymphoma samples. Our...
Cognate antigen recognition by CD4+ T cells is thought to contribute the tissue specificity of various autoimmune diseases, particularly those associated with class II MHC alleles. However, we show that localized MHC–dependent arthritis in F759 mice depends on local events result accumulation activated absence cognate recognition. In this model, transfer vitro polarized Th17 combined induction experimental microbleeding resulted CCL20 production, joints, and production IL-6. Disease required...
SummaryThe IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown amplifier is activated by of and STAT3 induces chemokines inflammation via an loop. However, its role human diseases unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association...
In this study, we investigated the relationship between several growth factors and inflammation development. Serum concentrations of epiregulin, amphiregulin, betacellulin, TGF-α, fibroblast factor 2, placental (PLGF), tenascin C were increased in rheumatoid arthritis patients. Furthermore, local blockades these suppressed development cytokine-induced mice by inhibiting chemokine IL-6 expressions. We found that epiregulin expression was early followed induction other at different sites...
Acute inflammation is the body's first defense in response to pathogens or injury that partially governed by a novel genus of endogenous lipid mediators orchestrate resolution inflammation, coined specialized pro-resolving (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include eicosapentaenoic acid-derived and docosahexaenoic Resolvins, Protectins, Maresins. Herein, we review their biosynthesis, structural characteristics, therapeutic effectiveness various diseases...
Although recent studies have identified regulatory roles for Foxp3+CD8+ T cells, the mechanisms that induce their development and underlie functions in vivo not been elucidated. Here, we show IL-6 positively regulates T-cell function. The cells differentiated vitro presence of suppressed autoimmune colitis arthritis vivo. Moreover, developed enhanced signaling a spontaneous Th17 cell-mediated arthritis. Thus, concluded develop response to regulate chronic inflammation F759 These results...
KDEL receptors are responsible for retrotransporting endoplasmic reticulum (ER) chaperones from the Golgi complex to ER. Here we describe a role receptor 1 (KDELR1) that involves regulation of integrated stress responses (ISR) in T cells. Designing and using an N-ethyl-N-nitrosourea (ENU)-mutant mouse line, T-Red (naïve T-cell reduced), show point mutation KDELR1 is reduction number naïve cells this model owing increase ISR. Mechanistic analysis shows directly regulates protein phosphatase...
RNA-binding motif 10 (Rbm10) is an protein that regulates alternative splicing, but its role in inflammation not well defined. Here, we show Rbm10 controls appropriate splicing of DNA (cytosine-5)-methyltransferase 3b (Dnmt3b), a methyltransferase, to regulate the activity NF-κB-responsive promoters and consequently development. deficiency suppressed NF-κB-mediated responses vivo vitro. Mechanistic analysis showed decreased promoter recruitment NF-κB, with increased methylation regions...
Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency skin disorders. Various cells including mast release Zn-containing granules when activated; however, the biological role of released Zn currently unclear. Here we report our findings that transporter ZnT2 required for from cells. In addition, found induce IL-6 production inflammatory such as fibroblasts promote wound healing, a process involves inflammation. induces variety pro-inflammatory cytokines through...
Abstract The breakpoint cluster region (BCR) is known as a kinase and cause of leukemia upon fusing to Abl kinase. In this study, we demonstrate that BCR associated with the α subunit casein II (CK2α), rather than itself, required for inflammation development. We found knockdown inhibited NF-κB activation in vitro vivo. Computer simulation, however, suggested putative domain has an unstable structure minimal enzymatic activity. Liquid chromatography–tandem mass spectrometry analysis showed...
For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise disease development examples of environment alterations which produce changes these networks. There indications that lipid metabolism contribute to the progression a variety cancers. Measuring such understanding pathways involved is critical fully understand...
In previous studies we demonstrated that chronic energy intake restriction (CEIR) by a diet relatively low in fat, high carbohydrate, and reduced 40% total calories extends life span delays development of autoimmune disease autoimmunity-prone mice. To investigate possible cellular basis for this dramatic action CEIR, analyzed the rate incorporation [3H]thymidine cells intestinal epithelium, thymus, spleen, mesenteric lymph nodes ad libitum-fed mice vs. CEIR three strains. New Zealand Black...
Abstract We recently reported that NF-κB–mediated inflammation caused by breakpoint cluster region (BCR) is dependent on the α subunit of casein kinase II (CK2α) complex. In current study, we demonstrate presenilin 1 (Psen1), which a catalytic component γ-secretase complex and mutations are known to cause familial Alzheimer disease, acts as scaffold BCR–CK2α–p65 induce NF-κB activation. Indeed, Psen1 deficiency in mouse endothelial cells showed significant reduction p65 recruitment target...
Abstract Type 1 diabetes (T1D) is most likely caused by killing of β cells autoreactive CD8+ T cells. Methods to isolate and identify these are limited their low frequency in the peripheral blood. We analyzed cells, reactive with Ags, cell libraries further characterized phenotype CyTOF using class I MHC tetramers. In libraries, islet Ag–specific CD45RO+IFN-γ+CD8+ was higher patients T1D compared healthy control subjects. Ag-specific from were ZnT8186–194, whereas those recognized...
Abstract Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination complex PRC1 in nucleus with no evidently direct link to NF-κB pathway. In this study, we report novel function of Bmi1: its regulation IκBα cytoplasm. A deficiency inhibited NF-κB–mediated gene expression vitro mouse model arthritis vivo. Mechanistic analysis showed associated SCF via N terminus phosphorylation by an IKKα/β-dependent pathway, leading IκBα. These effects on NF-κB–related inflammation...
Abstract Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident COVID-19, characteristics CTLs related to disease severity have not been fully explored. Here we show that phenotype against immunoprevalent epitopes COVID-19 convalescents might differ according course disease. We establish a cellular screening method uses artificial antigen presenting cells, expressing HLA-A * 24:02, costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S,...