A5076002314- Inflammatory Bowel Disease
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Digestive system and related health
- Microscopic Colitis
- T-cell and B-cell Immunology
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- IL-33, ST2, and ILC Pathways
- Genetic factors in colorectal cancer
- Liver Disease Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Gallbladder and Bile Duct Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Colorectal Cancer Treatments and Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Mesenchymal stem cell research
- Autoimmune and Inflammatory Disorders
- Cytokine Signaling Pathways and Interactions
- Tissue Engineering and Regenerative Medicine
- Cancer-related Molecular Pathways
- 3D Printing in Biomedical Research
Tokyo Medical and Dental University
2015-2024
The University of Tokyo
2016-2024
Toho University
2020-2024
Institute of Science Tokyo
2024
Tokyo Medical and Dental University Hospital
2022
Musashino Red Cross Hospital
2020-2021
Toho University Omori Medical Center
2020
Hospital Universitario de La Princesa
2015
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2015
Toxalim Research Centre in Food Toxicology
2015
Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that activated a greater number epithelial cells inflamed mucosa colitis. Inhibition activation vivo using gamma-secretase inhibitor resulted severe exacerbation colitis attributable loss regenerative response within layer. Activation supported by suppressing goblet...
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...
The transcription factor Atoh1/Hath1 plays crucial roles in the differentiation program of human intestinal epithelium cells (IECs). Although previous studies have indicated that Notch signal suppresses IEC, mechanism by which it does so remains unknown. This study shows undifferentiated state is maintained suppression Hath1 gene intestine. To assess effect signaling, doxycycline-induced expression intracellular domain (NICD) and Hes1 were generated LS174T. was analyzed quantitative...
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...
The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities CD4+ T cells in spinal cord their counterparts small intestine. Furthermore, unveil a synergistic relationship microbiota, particularly enriched with tryptophan metabolism gene EC:1.13.11.11, intestinal cells. This symbiotic collaboration results biosynthesis kynurenic acid (KYNA), which modulates recruitment...
Summary Background and Aims While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real‐world studies assessing its short‐ long‐term efficacy safety are limited. Methods This a multicenter, retrospective study of UC patients who started filgotinib between March 2022 September 2023. The primary outcome was clinical remission, defined as partial Mayo score ≤1 with rectal bleeding 0, or Simple Clinical...
Maintenance of the intestinal epithelium is based on well-balanced molecular mechanisms that confer stable and continuous supply specialized epithelial cell lineages from multipotent progenitors. Lineage commitment decisions in system involve multiple regulatory systems interplay with each other to establish cellular identities. Here, we demonstrate microRNA could be involved differentiation, microRNA-194 (miR-194) highly induced during this process. To investigate inducible expression...
Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, molecular basis of its production has remained totally unknown. We here showed that cells both constitutively when induced by gamma interferon (IFN-gamma) produced IL-7, while several other factors we tested had no effect. Transcriptional regulation via an IFN regulatory factor element (IRF-E) on 5' flanking region, which lacks canonical core...
Intestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also regeneration damaged intestinal epithelia. However, whether inflammatory environment Crohn's disease (CD) affects properties resident small remain uncertain.CD patient-derived organoids were established from enteroscopic biopsy specimens taken active lesions (aCD-SIO), or mucosa under remission (rCD-SIO). Expression ISC-marker genes those was examined by immunohistochemistry, microfluid-based...
ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, comprehensive contribution ATOH1+ IECs to homeostasis, repair, and tumorigenesis epithelium remains uncertain. Through our cell-lineage tracing, we show here that definite number retain stem cell properties can form ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) under completely homeostatic conditions. Interestingly, colonic appeared exhibit their function more...
Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality life. We evaluated the clinical characteristics perianal lesions in newly diagnosed CD patients and impact on life Japanese CD.
Abstract It is well known that immune responses in the intestine remain a state of controlled inflammation, suggesting not only does active suppression by regulatory T (TREG) cells play an important role normal intestinal homeostasis, but also its dysregulation response leads to development inflammatory bowel disease. In this study, we demonstrate murine CD4+CD25+ residing lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 suppress proliferation...
<h3>Objective</h3> Interleukin (IL)-7 is mainly produced in bone marrow (BM) that forms the niche for B cells. We previously demonstrated BM also retains pathogenic memory CD4 T cells murine models of inflammatory bowel disease (IBD). However, it remains unknown whether BM-derived IL-7 sufficient development IBD and which form colitogenic BM. <h3>Design</h3> To address these questions, we developed mice expression was specific BM, identified colitis-associated IL-7-expressing mesenchymal...