A5001269547- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Vasculitis and related conditions
- Inflammatory Myopathies and Dermatomyositis
- Cancer Immunotherapy and Biomarkers
- IgG4-Related and Inflammatory Diseases
- Salivary Gland Disorders and Functions
- Atherosclerosis and Cardiovascular Diseases
- Salivary Gland Tumors Diagnosis and Treatment
- Systemic Sclerosis and Related Diseases
- Lymphoma Diagnosis and Treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Glycosylation and Glycoproteins Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Periodontal Regeneration and Treatments
- Cancer-related molecular mechanisms research
- Immunodeficiency and Autoimmune Disorders
Kobe City Medical Center General Hospital
2020-2025
The University of Tokyo
2015-2024
Asahi University
1986-2019
RIKEN Center for Integrative Medical Sciences
2018
Mizuho (Japan)
2017
Sumitomo Dainippon Pharma (United States)
2015-2016
Kumamoto University
2016
Graduate School USA
2013
Tokyo Metropolitan Komagome Hospital
2008
Scripps Whittier Diabetes Institute
1995
Regulatory T cells (Tregs) are engaged in the maintenance of immunological self-tolerance and immune homeostasis. IL-10 has an important role maintaining normal state. Here, we show that IL-10-secreting Tregs can be delineated mice as CD4(+)CD25(-)Foxp3(-) express lymphocyte activation gene 3 (LAG-3), MHC-class-II-binding CD4 homolog. Although approximately 2% CD4(+)CD25(-) cell population consisted CD4(+)CD25(-)LAG3(+) spleen, enriched to 8% Peyer's patch. They hypoproliferative upon vitro...
Abstract Autoantibodies induce various autoimmune diseases, including systemic lupus erythematosus (SLE). We previously described that CD4 + CD25 − LAG3 regulatory T cells (LAG3 Treg) are regulated by Egr2, a zinc-finger transcription factor required for the induction of T-cell anergy. herein demonstrate Treg produce high amounts TGF-β3 in an Egr2- and Fas-dependent manner. require to suppress B-cell responses murine model lupus. Moreover, TGF-β3- Treg-mediated suppression requires PD-1...
Inhibitory cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), are humoral factors involved in the suppressive function of regulatory T cells play critical roles maintaining immune homeostasis. However, TGF-β IL-10 also have pleiotropic effects induce responses depending on conditions, thus their therapeutic application to autoimmune diseases remains limited. Here, we show that a combination IL-10, but not single cytokine, is required suppress B cell...
Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify cells that predict resistance.We isolated 18 55 patients with RA requiring addition new and 39 healthy controls, RNA sequencing. Transcriptome changes effects were systematically characterised. Association between gene modules resistance was evaluated. validated predictive value identified...
Interleukin-27 (IL-27) suppresses immune responses through inhibition of the development IL-17 producing Th17 cells and induction IL-10 production. We previously showed that forced expression early growth response gene 2 (Egr-2), a transcription factor required for T-cell anergy induction, induces lymphocyte activation 3 confers regulatory activity on CD4(+) T in vivo. Here, we evaluated role Egr-2 IL-27-induced Among various IL-10-inducing factors, only IL-27 induced high levels expression....
Abstract Splicing quantitative trait loci (sQTLs) are one of the major causal mechanisms in genome-wide association study (GWAS) loci, but their role disease pathogenesis is poorly understood. One reason complexity alternative splicing events producing many unknown isoforms. Here, we propose two approaches, namely integration and selection, for this by focusing on protein-structure First, integrate isoforms with same coding sequence (CDS) identify 369-601 integrated-isoform ratio QTLs (i 2...
Objective Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease. While long-term prognosis has greatly improved, better survival still necessary. The type I interferon (IFN) signature, a prominent feature of SLE, not an ideal therapeutic target or outcome predictor. To explore immunological pathways in SLE more precisely, we performed transcriptomic, epigenomic and genomic analyses using 19 immune cell subsets from peripheral blood. Methods We sorted identified...
Abstract Introduction Anti-citrullinated protein/peptide antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA) patients and thought have a close relationship with the pathogenesis of arthritis. Several proteins, including fibrinogen, vimentin, alpha-enolase, were reported as ACPA-target antigens, their importance in RA was widely proposed. We identified citrullinated immunoglobulin binding protein (citBiP) another ACPA target examined its pro-inflammatory role Methods measured...
Significance Transcription factors early growth response gene 2 (Egr2) and Egr3 have long been regarded as negative regulators of T-cell activation. Egr2 is also known a susceptibility for systemic lupus erythematosus characterized by dysregulated humoral immune responses to autoantigens. Previously, we reported that Egr2-expressing CD4 + CD25 - LAG3 regulatory T cells regulate pathogenesis via production TGF-β3. However, the role in regulation immunity unclear. Here report germinal center...
Regulatory T cells (Tregs) play a role in the suppression of inflammation autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as marker interleukin (IL)-10-producing Tregs. We aimed to clarify function human IL-10-producing CD4+CD25-LAG3+ (LAG3+ Tregs) their association with rheumatoid arthritis (RA).LAG3+ Tregs peripheral blood mononuclear (PBMCs) were cultured B follicular helper examine antibody effects. The frequency LAG3+ evaluated samples from 101 healthy donors...
Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus strongest genetic risk factor for rheumatoid arthritis, relationship between alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients 110 healthy donors. The frequency memory CXCR4 + CD4 T not Th1 Th17 cells, was significantly associated with...
Objectives Synovial fibroblasts (SFs) are one of the major components inflamed synovium in rheumatoid arthritis (RA). We aimed to gain insight into pathogenic mechanisms SFs through elucidating genetic contribution molecular regulatory networks under inflammatory condition. Methods from RA and osteoarthritis (OA) patients (n=30 each) were stimulated with eight different cytokines (interferon (IFN)-α, IFN-γ, tumour necrosis factor-α, interleukin (IL)-1β, IL-6/sIL-6R, IL-17, transforming...
The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) maintenance phase are unknown. Here, we collected blood samples from SLE (n=44) treated before and three six months after treatment. RNA-Seq whole was performed, gene expression quantified. Immune cell type enrichment analysis estimated immune subtype proportions each subtype. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) < 4 at set as primary...
Abstract Objectives To identify unmet medical needs (UMNs) of practices and investigate the real-world prescribing therapeutic treatments test implementation for patients with juvenile idiopathic arthritis (JIA). Methods Possible UMNs were collected from eight pediatric adult rheumatologists. verify UMNs, JIA described using National Database Health Insurance Claims Specific Checkups Japan (NDB). Results Fifty-eight possible 16 experts 35 investigated NDB. The highest priority was expansion...
Abstract Patients with autoimmune and autoinflammatory diseases experience difficult physical, mental, social situations have various unmet medical needs (UMNs). To provide appropriate solutions for these patients, an accurate understanding of their UMNs is necessary. Patient-reported outcomes (PROs) reflect the problems patients are highly likely to be useful in patient needs. This article reviews established PRO measures from perspective determining those identifying diseases. consider...
Abstract Objectives: This study aims investigates real-world data on the demographics, prescribing practices, and healthcare costs of juvenile idiopathic arthritis (JIA) with polyarthritis or oligoarthritis compared to rheumatoid (RA) patients in adolescents young adults. Methods: Data from Japan Medical Center (JMDC) claims database for fiscal years (FY) 2016–2020 were analyzed. JIA RA defined as having at least 2 months disease-modifying antirheumatic drug (DMARD) prescriptions...
A 62-year-old man developed a fever, fatigue, anorexia and arthralgia. Central hypocorticoidism central hypothyroidism were observed, low serum antidiuretic hormon level without symptoms of diabetes insipidus, as well. Images showed swelling pituitary stalk, mediastinal hilar lymphnodes pancreas, pulmonary infiltrates retroperitoneal mass. Serum CRP was 20.6 mg/dL, IgG4 292 mg/dL. Lung biopsy revealed pseudotumor containing IgG4-positive plasmacytes, obliterative vasculitis both in...
Objectives: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate clinical characteristics and efficacy immunosuppressive treatment exacerbated RA-ILD. Methods: Clinical data, including respiratory function, imaging, treatment, prognosis, were retrospectively collected for 17 patients with who required...
Obesity is associated with worse disease activity and drug responses in patients rheumatoid arthritis (RA). However, the immunological mechanisms responsible for relationship between RA obesity have not yet been clarified detail. This study aimed to elucidate contributing pathogenesis of overweight patients.The frequencies CD4+ T cell, B cell monocyte subsets were analyzed (n = 81) healthy donors 99) by flow cytometry, compared three groups (body mass index (BMI) <20, ≥20 25, >25). Serum...
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory immune system and reported to inhibit B cell function both mice humans. Recently, it suggested that TGF-β3 may play role regulation mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress through production TGF-β3, therapeutic mouse model systemic lupus erythematosus. The effect on human not reported, we herein examined cells....