A5002572299- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Asthma and respiratory diseases
- Eosinophilic Esophagitis
- Rheumatoid Arthritis Research and Therapies
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Psoriasis: Treatment and Pathogenesis
- Mast cells and histamine
- Dermatology and Skin Diseases
- Chronic Lymphocytic Leukemia Research
- Antimicrobial Peptides and Activities
- Gastroesophageal reflux and treatments
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Microtubule and mitosis dynamics
- Urticaria and Related Conditions
- Aldose Reductase and Taurine
- Biomarkers in Disease Mechanisms
- Systemic Sclerosis and Related Diseases
Hamamatsu Medical Center
2018-2023
Chiba University
2012-2022
Chiba University Hospital
2012-2020
National Institutes of Health
2008-2010
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2008-2010
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2009
The interleukin (IL) 17 family of cytokines has emerged to be critical for host defense as well the pathogenesis autoimmune and autoinflammatory disorders, serves link adaptive innate responses. Recent studies have identified a new subset T cells that selectively produce IL-17 (Th17 cells; Bettelli, E., T. Korn, V.K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652–657; Kolls, J.K., A. Linden. 2004. Immunity. 21:467–476), but regulation production by immune is less understood. We report in vitro...
Abstract Objective The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) refer to a possible use ultrasound “for confirmation the clinical findings.” We undertook this study determine optimized definition ultrasound‐detected synovitis ACR/EULAR and assess impact its on accuracy RA classification. Methods One hundred nine patients with musculoskeletal symptoms ≤3 years were enrolled in study. Patients...
Stat3 signaling is essential for the induction of RORγt and subsequent Th17 cell differentiation. However, downstream targets expression remain largely unknown. We show here that a novel isoform Sox5, named Sox5t, induced in cells Stat3-dependent manner. In vivo, T cell-specific Sox5-deficient mice exhibit impaired differentiation are resistant to experimental autoimmune encephalomyelitis delayed-type hypersensitivity. Retrovirus-mediated Sox5 together with c-Maf induces even Stat3-deficient...
Helios+FoxP3+CD4+ (Helios+) Treg cells are believed to be involved in the regulation of various autoimmune diseases; however, regulatory mechanisms underlying development Helios+ remain uncertain. This study was undertaken elucidate Helios expression CD4+ T and its roles transforming growth factor β (TGFβ)-induced cell function.We examined patients with rheumatoid arthritis by DNA microarray analysis before after treatment biologic agents. We also effect interleukin-6 (IL-6) TGFβ on humans...
The guanine nucleotide exchange factor Brx is essential for osmotic stress–mediated expression of nfat5 in lymphocytes.
Abstract Background Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger mitotic entry and mediates destruction mitosis inhibitory kinase. Little is known about relevance CDCA3 human malignancy including oral squamous cell carcinoma (OSCC). We aimed characterize expression state function in OSCC. Methods evaluated mRNA protein both OSCC-derived lines primary OSCCs performed functional analyses cells using shRNA system. Results...
Abstract It is well known that sensitization against fungi closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component β-glucan, as some component(s) in house dust mite (HDM) extract. However, roles HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1–deficient (Clec7a−/−) mice to examine whether involved inflammation. We found eosinophil and neutrophil recruitment into...
The tumor suppressor p53 plays a central role in suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair. In addition to the antitumor functions of p53, accumulating evidence using systemic p53-deficient mice suggests that suppresses autoimmunity. However, it remains unknown how this study, we generated T cell-specific (CD4-Cre p53(fl/fl) mice, or conditional knockout [cKO] mice) found aged p53-cKO spontaneously developed inflammatory lesions various organs,...
Cell division cycle associated 2 (CDCA2) recruits protein phosphatase 1 to chromatin antagonize activation of ataxia telangiectasia mutated (ATM)-dependent signal transduction. ATM kinase plays a critical role in the DNA damage response and its phosphorylation cascade inhibit p53-MDM2 interaction, which releases p53 induce p21 G1 cell-cycle arrest. However, relevance CDCA2 human malignancy including oral squamous cell carcinoma (OSCC) is unknown. In current study, we found that expression...
We recently showed that mice lacking B and T lymphocyte attenuator (BTLA), a third inhibitory coreceptor expressed on cells cells, exhibit an increased Ag-specific IgG response gradually develop hyper-gamma-globulinemia autoantibody production. Recent studies revealed follicular Th (Tfh) which are non-Th1, non-Th2 effector express CXCR5 provide help for to produce Ig, also BTLA. However, the role of BTLA in Tfh cell function remains unknown. In this study, we examined regulatory development...
Annexins are calcium and phospholipid binding proteins that form an evolutionary conserved multigene family. Considerable evidence indicates annexin A10 (ANXA10) is involved in tumoral progression, although little known about its role human oral carcinogenesis. In this study, we investigated the involvement of ANXA10 squamous cell carcinoma (OSCC).ANXA10 mRNA protein expressions were assessed by quantitative reverse transcriptase polymerase chain reaction immunoblotting, conducted a...
Previous studies have shown that IL-22, one of the Th17 cell–related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, underlying mechanism remains unclear. Here, we show and cytokine production upon intratracheal administration house dust mite (HDM) extract, a representative allergen, were exacerbated IL-22-deficient mice. We also found IL-22 induces Reg3γ from lung epithelial cells through STAT3 activation...
Increasing evidence has revealed that mast cell–derived tumor necrosis factor α (TNF-α) plays a critical role in number of inflammatory responses by recruiting leukocytes. In this paper, we investigated the regulatory interleukin 4 (IL-4) TNF-α production cells. IL-4 inhibited immunoglobulin E–induced and neutrophil recruitment peritoneal cavity wild-type mice but not signal transducers activators transcription 6 (Stat6)–deficient mice. also cultured cells Stat6-dependent mechanism....
The zinc finger protein 36-like 2, ZFP36L2, is a member of small family RNA-binding proteins composed by ZFP36 (also known as tristetraprolin, TTP), ZFP36L1 and ZFP36L2 in humans, with corresponding murine orthologs. These bind to adenine uridine-rich element (ARE) the 3'untranslated region target messenger RNA stimulate degradation. functions an anti-inflammatory modulator models inflammatory diseases down-regulating production cytokines such tumor necrosis factor-α. However, how alter...
Abstract In previous studies, we have shown that Th2 cell differentiation is diminished but Th1 increased in Stat5a-deficient (Stat5a−/−) CD4+ T cells. the present study, clarified molecular mechanisms of Stat5a-mediated Th differentiation. We found enhanced and resultant IFN-γ production played a dominant inhibitory role down-regulation IL-4-induced Stat5a−/− also IL-12-induced Stat4 phosphorylation were augmented Importantly, expression suppressor cytokine signaling (SOCS)3, potent...
Abstract It is well-recognized that Stat6 plays a critical role in Th2 cell differentiation and the induction of allergic inflammation. We have previously shown Stat5a also required for airway However, it relative importance redundancy inflammation are unknown. In this study we addressed these issues by comparing Stat5a-deficient (Stat5a−/−) mice, Stat6−/− Stat5a- double-deficient (Stat5a−/− Stat6−/−) mice on same genetic background. was severely decreased Stat6−/−CD4+ T cells, but...
Comparative studies using Th2-prone BALB/c and Th1-prone C57BL/6 mice were performed to clarify the influence of genetic background on Th cell differentiation. The results showed IL-4, production which is induced by IL-2, be much more abundantly produced naive CD4+ T cells than cells, thereby leading a tendency for differentiation toward Th2 in cells. This difference IL-4 between two appeared attributable specific intracellular signaling events. Signal transducer activator transcription 5...