A5030148991- Immune Cell Function and Interaction
- Inflammatory Bowel Disease
- T-cell and B-cell Immunology
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Helicobacter pylori-related gastroenterology studies
- Microscopic Colitis
- Autophagy in Disease and Therapy
- IL-33, ST2, and ILC Pathways
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Mycobacterium research and diagnosis
- Digestive system and related health
- Pharmacological Effects of Natural Compounds
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Veterinary medicine and infectious diseases
- Gut microbiota and health
- Eosinophilic Esophagitis
- Gastrointestinal disorders and treatments
- Apelin-related biomedical research
Tokyo Medical and Dental University
2012-2024
The University of Tokyo
2014-2024
Graduate School USA
2015
Brigham and Women's Hospital
2003-2010
Harvard University
2003-2010
Harvard University Press
2003-2008
Nihon University
1994-1999
Treatment with anti-TNF-alpha MAb has been accepted as a successful maintenance therapy for patients inflammatory bowel diseases (IBD). Moreover, it recently reported that blockade of TNF receptor (TNFR) 1 signaling in infiltrating hematopoietic cells may prevent the development colitis-associated cancer (CAC). However, remains unclear whether TNF-alpha epithelial is involved CAC. To investigate this, we studied effects an animal model CAC by administration azoxymethane (AOM) followed...
Autophagy plays important roles in metabolism, differentiation, and survival T cells. TNFAIP3/A20 is a ubiquitin-editing enzyme that thought to be negative regulator of autophagy cell lines. However, the role TNFAIP3 remains unclear. To determine whether regulates CD4 cells, we first analyzed Tnfaip3-deficient naïve cells vitro. We demonstrated exhibited reduced MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) puncta formation, increased mitochondrial content, exaggerated...
Ubiquitination is a crucial post-translational modification; however, the functions of ubiquitin-coding genes remain unclear. UBA52 encodes fusion protein comprising ubiquitin at N-terminus and ribosomal L40 (RPL40) C-terminus. Here we showed that Uba52-deficient mice die during embryogenesis. UBA52-deficient cells exhibited normal levels total ubiquitin. However, displayed decreased synthesis cell-cycle arrest. The overexpression ameliorated arrest caused by deficiency. Surprisingly, RPL40...
Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface that has been proposed to negatively regulate T function. We have shown CEACAM1 associated with specific regulation of helper (Th)1 pathways, T-bet–mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated anti–mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited reduced severity trinitrobenzene sulfonic acid colitis association decreased...
Abstract Carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) consists of highly related homologs in humans and rodents that are characterized by significant alternate splicing generating isoforms capable negative intracellular signaling virtue two immunoreceptor tyrosine-based inhibition motifs its cytoplasmic (cyt) tail. Although human T cells have been recently observed to express CEACAM1, the expression function CEACAM1 mouse not defined. resting spleen exhibited no evidence on...
Abstract The long cytoplasmic tail (CT) isoforms of carcinoembryonic Ag-related cell adhesion molecule 1 (CEACAM1) are expressed on activated human T cells and possess two ITIM motifs in the CT. These CEACAM1 inhibitory for responses initiated by TCR/CD3 complex with inhibition dependent upon ITIMs Src homology 2 domain-containing phosphatase (SHP-1). However, mechanism which this occurs is unknown. We demonstrate here that family kinase, Lck, ability to bind homophilically required...
Objective Although immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried elucidate effect IgA on homeostasis maintenance mechanism. Design We generated various mutant mouse lines using CRISPR/Cas9 genome editing system. Then, evaluated small intestinal homeostasis, pathology, microbiota, cytokine production, immune cell activation intravital...
Abstract Carcinoembryonic Ag-related cellular adhesion molecule 1 (CEACAM1) represents a group of transmembrane protein isoforms that consist variable numbers extracellular Ig-like domains together with either long cytoplasmic (cyt) tail containing two immunoreceptor tyrosine-based inhibitory motifs or unique short cyt tail. Although CEACAM1 has been reported to be expressed on the surface T lymphocytes upon activation, its roles in cell regulation are controversial due lack functional...
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It has been suggested that prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). We previously observed the NF-κB activation in colonic epithelial cells is associated with increased tumor necrosis factor receptor 2 (TNFR2) expression CAC development. However, mechanism by which leading still unclear. Myosin light chain kinase (MLCK) reported be responsible for permeability TNF signaling. Therefore we focused on role of MLCK via TNFR2 signaling...
Background & AimsMucosal-associated invariant T (MAIT) cells are innate-like restricted by major histocompatibility complex-related molecule 1 (MR1) and express a semi-invariant cell receptor. Previously, we reported the activation status of circulating MAIT in patients with ulcerative colitis (UC) was associated disease activity that these had infiltrated inflamed colonic mucosa. These findings suggest involved pathogenesis inflammatory bowel disease. We investigated role using MR1−/− mice...
Granulomas represent a localized inflammatory reaction that is characteristically observed in many conditions. However, the mechanisms of granuloma formation have not been fully defined. Herein we demonstrate, by using experimental models intestinal inflammation, unique CD11c+ DC-like cell subset exhibits phenotypic and functional features immature myeloid DCs characterized expression macrophage marker (F4/80) produces large amounts IL-23 directly induces development granulomas under...
The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I-related molecule known to protect IgG and albumin from catabolism transport across polarized epithelial cells in bidirectional manner. Previous studies have shown species-specific differences ligand binding, direction, steady-state membrane distribution when expressed cells. We hypothesized that these may be due the additional N-glycans on rat FcRn, because been proposed function as apical targeting signals, two of...
It has been recently demonstrated that NKG2D is an activating costimulatory receptor on natural killer (NK) cells, T (NKT) activated CD8(+) and gammadelta which respond to cellular stress, such as inflammation, transformation, infection. Here we show intestinal inflammation in colitic SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) cells characterized significant increase CD4(+)NKG2D(+) constitutive expression ligands, H60, Mult-1, Rae-1, lamina propria CD11c(+) dendritic cells....
Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as split fluorescent protein. The PolyUb-FC has advantage that monoubiquitination is nonfluorescent chain-specific polyubiquitination can be directly visualized in living cells without antibodies. applied to examine K33-linked...
Background & AimsThe reason why small intestinal cancer is rarer than colorectal not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the intestine, closest immune cells to epithelial cells, exclude tumor via cell-to-cell contact.MethodsWe developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple neoplasia (APCmin ) mice, a T-cell–reporter mouse with spontaneous tumors. visualized dynamics of IELs microenvironment and...
Patients with inflammatory bowel disease ( IBD ) have an increased risk of developing colitis‐associated colorectal cancer CAC ). cells often develop chemoresistance, resulting in a poorer prognosis than that sporadic CRC The mechanism by which enhances malignant potential remains unknown. We previously reported the proteasomal degradation transcription factor Atonal homolog 1 (Atoh1) protein results non‐mucinous form . It also unknown whether Atoh1 is expressed Therefore, present study, we...