A5028974310- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Rheumatoid Arthritis Research and Therapies
- Systemic Sclerosis and Related Diseases
- Inflammatory Myopathies and Dermatomyositis
- Pulmonary Hypertension Research and Treatments
- Autoimmune and Inflammatory Disorders Research
- Immunodeficiency and Autoimmune Disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Skin Diseases and Diabetes
- Eosinophilic Disorders and Syndromes
- Cardiac electrophysiology and arrhythmias
- Diabetes and associated disorders
- Atherosclerosis and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- Renal Diseases and Glomerulopathies
- Venous Thromboembolism Diagnosis and Management
- Liver Disease Diagnosis and Treatment
- Advanced MRI Techniques and Applications
- Immunotherapy and Immune Responses
- Vasculitis and related conditions
- Tracheal and airway disorders
- Ultrasound and Hyperthermia Applications
- Immune cells in cancer
Hokkaido University
2016-2025
Kishiwada Tokushukai Hospital
2019-2025
Fukuoka Tokushukai Hospital
2024-2025
GTx (United States)
2024
Beth Israel Deaconess Medical Center
2016-2022
Harvard University
2016-2022
Sapporo University
2021
National Institute of Technology, Tomakomai College
2018
Obihiro Kosei General Hospital
2016-2017
Hokkaido University Hospital
2016
Abstract Dysregulation of Th17 and Treg cells contributes to the pathophysiology many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits cell differentiation promotes by orchestrating metabolic epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis oxidative phosphorylation in Th17- Treg-polarizing T cells. Following treatment with S-adenosyl-L-methionine/S-adenosylhomocysteine ratio 2-hydroxyglutarate levels are decreased...
Objective. Interstitial lung diseases (ILDs) complicated with PM or DM are frequently aggressive and refractory to treatment. Recently some reports have suggested the potential benefit of tacrolimus for severe ILD PM/DM. However, little evidence has yet shown efficacy in these settings. The aim this study was evaluate as a treatment PM-/DM-related ILD. Methods. This retrospective comprised 49 previously untreated patients diagnosed admitted Hokkaido University Hospital from January 2000 July...
Significance Th17 cells unlike other CD4 + T helper subsets use glutaminolysis as a source of energy and upregulate Gls1. Inhibition Gls1 ameliorates differentiation in vitro experimental autoimmune encephalomyelitis mice. Mechanistically this is accomplished through the upregulation by Th17-promoting transcription factor, inducible cAMP early repressor (ICER). These findings claim an essential role generation offer approach to control diseases linked their generation.
Podocyte malfunction occurs in autoimmune and nonautoimmune kidney disease. Calcium signaling is essential for podocyte injury, but the role of Ca2+/calmodulin-dependent kinase (CaMK) podocytes has not been fully explored. We report that from patients with lupus nephritis focal segmental glomerulosclerosis lupus-prone lipopolysaccharide- or adriamycin-treated mice display increased expression CaMK IV (CaMK4), CaMK2. Mechanistically, CaMK4 modulated motility by altering GTPases Rac1 RhoA...
Th1 and Th17 are important in the pathogenesis of autoimmune diseases they depend on glycolysis as a source energy. T cell antigen receptor signaling phosphorylates serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), promotes glycolysis. Based these findings we hypothesized that CaMK4 Camk4-deficient CD4+ cells treated with inhibitor had less compared their counterparts. Pull-down mass spectrometry identified pyruvate muscle isozyme (PKM), final rate-limiting...
Glutaminase 1 (Gls1) is the first enzyme in glutaminolysis. The selective Gls1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) suppresses Th17 development and ameliorates experimental autoimmune encephalomyelitis (EAE). present study was undertaken to investigate whether inhibition of glutaminolysis beneficial for treatment systemic lupus erythematosus (SLE), involved mechanisms.MRL/lpr mice were treated with BPTES or vehicle control, disease activity examined....
Inducible cAMP early repressor (ICER) has been described as a transcriptional isoform of the response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through IL-6-STAT3 pathway and binds to Il17a promoter, where it facilitates accumulation canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4+ T impaired but can be rescued by forced overexpression ICER. Consistent with role autoimmune inflammatory diseases, B6.lpr...
Significance Th17 cells favor glycolytic metabolism. Pyruvate dehydrogenase, which facilitates entry into the oxidative phosphorylation circle, is inhibited by pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2). Our studies demonstrate that transcription factor ICER/CREM, known to promote differentiation and related pathology, suppresses expression of PDP2 diverts energy production pathway. In lupus-prone mice people with systemic lupus erythematosus, levels are decreased its...
The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according International Society Nephrology and Renal Pathology classification. This retrospective analysis comprised 186 Japanese given a diagnosis LN by renal specimen mean observation period 12 years. Primary end point defined as death or end-stage disease, standardized mortality ratios were calculated. Five presented histopathological class I, 62 II, 21 III III+V, 73 IV IV+V 25 V....
Significance Systemic lupus erythematosus (SLE) is characterized by compromised IL-2 production and regulatory T-cell function. Studies in human SLE murine models report that replenishment ameliorates clinical manifestations. Here we show engagement of signaling lymphocytic activation molecule family 3 (SLAMF3), a coregulatory receptor T cells, restores the sensitivity CD4 + cells to IL-2, increasing their response exogenous via up-regulation IL-2Rα subunit. Moreover, naïve with monoclonal...
Abstract Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve cells undergo rapid proliferation, differentiation cytokine production. Since initial report, approximately two decades ago, that engagement CD28 enhances glycolysis but PD-1 CTLA-4 decrease it, significant information has been generated which linked metabolic reprogramming with fate differentiating health autoimmunity. Herein we...
Abstract Objective Using cluster analysis, to identify the subgroup of patients with APS poorest prognosis and clarify characteristics that subgroup. Methods This is a longitudinal retrospective cohort study patients. clinical data profile aPL, analysis was performed classify into subgroups. Events were defined as thrombosis, severe bleeding, mortality. Results A total 168 included. Cluster classified three subgroups; (n = 61): secondary APS, B 56): accumulation cardiovascular risks arterial...
Nintedanib is an inhibitor of tyrosine kinases that has been shown to slow the progression interstitial lung disease (ILD), including ILD associated with SSc. The aim this study was explore effect nintedanib on cardiomyopathy systemic sclerosis (SSc).Twenty consecutively hospitalized patients SSc-ILD were enrolled and prospectively followed. rate change at 6 months in cardiac magnetic resonance (CMR) parametric mapping, myocardial extracellular volume, primarily evaluated. Other endpoints...
Gastrointestinal stromal tumors (GISTs) arising within hepatic round ligament cysts are exceptionally rare, with limited literature available [1], hence making their definitive diagnosis challenging. Detective flow imaging (DFI) is a novel endoscopic ultrasound (EUS) modality for differentiating malignancies by evaluating irregular vessels [2] [3] [4] [5]. We report case in which DFI was crucial benign and malignant lesions, leading to of GIST cyst.
Abstract Objectives Recent guidelines and recommendations for lupus nephritis (LN) suggest rapid glucocorticoid (GC) reduction; however, robust supporting evidence remains limited. This study aimed to evaluate the impact of GC reduction on renal outcomes in patients with proliferative LN. Methods We conducted a multicentre retrospective chart review GC-naïve, biopsy-proven LN available urinary protein-to-creatinine ratio (UPCR) data before 52 weeks after treatment. Patients who reduced their...