A5054380036- Immune Cell Function and Interaction
- Liver Disease Diagnosis and Treatment
- Liver Diseases and Immunity
- Liver physiology and pathology
- Immunotherapy and Immune Responses
- Genomics, phytochemicals, and oxidative stress
- Immune Response and Inflammation
- Gut microbiota and health
- Hepatitis C virus research
- Psoriasis: Treatment and Pathogenesis
- Inflammatory Bowel Disease
- Dermatology and Skin Diseases
- T-cell and B-cell Immunology
- Tryptophan and brain disorders
- Glycosylation and Glycoproteins Research
- Asthma and respiratory diseases
- Pediatric Pain Management Techniques
- Traditional Chinese Medicine Studies
- Eosinophilic Esophagitis
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Galectins and Cancer Biology
- Clinical Nutrition and Gastroenterology
- Drug-Induced Hepatotoxicity and Protection
- Adipokines, Inflammation, and Metabolic Diseases
Mitsubishi Tanabe Pharma Corporation
2017-2024
Keio University
2017-2023
Mitsubishi Group (Japan)
2017-2020
Osaka University
2019
Abstract Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease that can progress to fibrosis. Recent clinical advance suggests reversibility fibrosis, but the cellular and molecular mechanisms underlying NASH resolution remain unclarified. Here, using murine diet-induced subsequent model, we demonstrate direct roles CD8 + tissue-resident memory T (CD8 Trm) cells in resolving Single-cell transcriptome analysis FACS revealed CD69 CD103 − Trm cell enrichment livers....
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...
Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for tolerance concanavalin A-induced Acute injury resulted enrichment commensal Lactobacillus gut. Notably, activated IL-22 production by gut lymphoid and raised...
Psoriasis and inflammatory bowel disease (IBD) are both chronic diseases occurring in the skin gut, respectively. It is well established that psoriasis IBD have high concordance rates, similar changes immune cells microbiome composition been reported conditions. To study this connection, we used a combination murine model of psoriatic dermatitis colitis which mice were treated topically with Toll-like receptor 7 agonist imiquimod (IMQ) fed dextran sulfate sodium (DSS).We applied IMQ to B6...
Acute liver failure (ALF) is a life-threatening condition, and transplantation the only therapeutic option. Although immune dysregulation central to its pathogenesis, precise mechanism remains unclear. Here, we show that number of peripheral hepatic plasmacytoid DCs (pDCs) decrease during acute injury in both humans mice. Selective depletion pDCs Siglechdtr/+ mice exacerbated concanavalin A-induced injury. In contrast, adoptively transferred BM-derived preferentially accumulated inflamed...
IL-10 is an immune regulatory cytokine and its genetic defect leads to gastrointestinal inflammation in humans mice. Moreover, the IL-23/Th17 axis known be involved these inflammatory disorders. IL-17A, a representative produced by Th17 cells, has important role for pathological process of diseases. However, precise function IL-17A bowel disease (IBD) remains controversial. In this study, we evaluated effect on colitis IL-10-deficient (Il10-/-) Mice lacking both (Il10-/-Il17a-/-) suffered...
We previously showed that knockdown of nuclear factor E2-related 2 (Nrf2) resulted in suppression hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. The effect brusatol investigated by analyzing HCV RNA proteins a hepatic cell line persistently-infected with HCV, HPI cells, replication replicon-replicating line, OR6 cells. Then, enhancement the combination drugs including sorafenib, which been reported...
The fate of resolution liver fibrosis after withdrawal injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts pro-fibrogenic. After injury, we unexpectedly observed a significant delay as TLR4 signaling was pharmacologically inhibited vivo two murine models. Single-cell transcriptome analysis hepatic CD11b+ cells, main producers matrix metalloproteinases (MMPs), revealed prominent cluster restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed gut...
Plasmacytoid dendritic cells (pDCs) perform dual proinflammatory and immunosuppressive roles. We recently reported the potential of pDC therapy for treatment intractable acute liver failure. However, establishment efficient methods to deliver pDCs is essential future clinical therapeutic applications. The present study demonstrates a higher abundance peripheral blood in mice lacking C-C motif chemokine receptor 9 (CCR9), gut-homing receptor, than WT mice. Adoptive transfer Ccr9-/- resulted...
Abstract Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help maintaining intestinal homeostasis. Peripheral CD4 + T cells can develop into CD8αα IELs upon arrival at epithelium via lamina propria (LP). Although this specific differentiation of is well established, mechanisms preventing it from occurring LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression low IELs, but CCR9 deficiency results over-differentiation both and...
Background Liver fibrosis is one of the cardinal clinical features chronic hepatitis C (CHC). However, mechanisms underlying evolution and reversion liver after virus (HCV) eradication their relationship with outcomes metabolic alterations are not fully elucidated. Whether any non-invasive marker can predict prognosis unknown. Methods Between October 2014 September 2019, 418 patients CHC or compensated cirrhosis HCV were prospectively recruited in this observational study. 326 that...
Background & AimsB-cell depletion therapy with an anti-CD20 is effective treatment strategy for patients refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear.MethodsHerein, we used adeno-associated virus IL-12 model, in which hepatic expression triggers liver injuries characteristic of AIH. We also analysed clinical samples AIH.ResultsB-cell using or splenectomy was found to improve functions and decrease cytotoxic CD8+ T-cell (cytotoxic T...