A5101699247- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Nuclear Receptors and Signaling
- Cytokine Signaling Pathways and Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Macrophage Migration Inhibitory Factor
- Immunotherapy and Immune Responses
- Multiple Sclerosis Research Studies
- Antibiotics Pharmacokinetics and Efficacy
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Whipple's Disease and Interleukins
- Monoclonal and Polyclonal Antibodies Research
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Systemic Lupus Erythematosus Research
- Autoimmune and Inflammatory Disorders Research
- Metabolism and Genetic Disorders
- Epilepsy research and treatment
- Lymphoma Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- Gastrointestinal Tumor Research and Treatment
- Retinoids in leukemia and cellular processes
- Nerve injury and regeneration
- PI3K/AKT/mTOR signaling in cancer
National Center of Neurology and Psychiatry
2014-2024
John Wiley & Sons (United States)
2024
Hudson Institute
2024
Institute of Science Tokyo
2022
Fukushima Medical University
2003-2021
National Neuroscience Institute
2009-2016
Osaka University
2008
Hiroshima City Asa Citizens Hospital
2005
Columbia University
2002-2004
Tokyo Metropolitan Children's Medical Center
1999-2000
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. Foxp3+ regulatory (Treg) cells are reduced in frequency and dysfunctional patients with MS, but underlying mechanisms this deficiency unclear. Here, we show that induction human IFN-γ-IL-17A-Foxp3+CD4+ inhibited presence circulating exosomes from MS. The exosomal miRNA profile MS differs healthy controls, let-7i, which markedly increased suppresses Treg by targeting insulin like growth factor 1...
OCH, a sphingosine-truncated analog of α-galactosylceramide (αGC), is potential therapeutic reagent for variety Th1-mediated autoimmune diseases through its selective induction Th2 cytokines from natural killer T (NKT) cells. We demonstrate here that the NKT cell production IFN-γ more susceptible to sphingosine length glycolipid ligand than IL-4 and chain determines duration stimulation by CD1d-associated glycolipids. Furthermore, cells requires longer receptor required stimulated either...
OCH, a sphingosine-truncated analog of α-galactosylceramide (αGC), is potential therapeutic reagent for variety Th1-mediated autoimmune diseases through its selective induction Th2 cytokines from natural killer T (NKT) cells. We demonstrate here that the NKT cell production IFN-γ more susceptible to sphingosine length glycolipid ligand than IL-4 and chain determines duration stimulation by CD1d-associated glycolipids. Furthermore, cells requires longer receptor required stimulated either...
Abstract Development of acute experimental autoimmune encephalomyelitis (EAE) depends on Th17 cells expressing the nuclear factor NR4A2. However, in mice lacking NR4A2 T cells, a late-onset disease is still inducible, despite great reduction inflammation. We here reveal that development this late onset cytotoxic T-cell-like CD4 + T-box transcription Eomesodermin (Eomes). T-cell-specific deletion Eomes gene remarkably ameliorates EAE. Strikingly, similar are increased peripheral blood and...
Multiple sclerosis (MS), a putative autoimmune disease of the central nervous system (CNS), commonly presents as relapsing-remitting MS (RRMS), characterized by recurrent episodes peripheral disabling symptoms resulting from inflammatory CNS damage. Many RRMS patients transition to chronic course with progressive neurological dysfunctions (secondary MS, SPMS), progression rate varying between and over time. SPMS pathogenesis is now linked immune-cell-mediated processes, although mechanisms...
Abstract Objective OCH, a synthetic analog of α‐galactosylceramide with truncated sphingosine chain, stimulates natural killer T (NKT) cells to produce predominantly Th2 cytokines. Thus, OCH may be potential agent for the treatment Th1‐mediated autoimmune diseases. This study was designed evaluate protective effects on collagen‐induced arthritis (CIA) in mice. Methods Mice were immunized type II collagen (CII) and injected intraperitoneally twice per week before or after onset CIA. They...
Abstract Although invariant NKT (iNKT) cells play a regulatory role in the pathogenesis of autoimmune diseases and allergy, an initial trigger for their responses remains elusive. In this study, we report that proportion human CD4+ iNKT cell clones produce enormous amounts IL-5 IL-13 when cocultured with CD1d+ APC presence IL-2. Such bias was never observed stimulated same α-galactosylceramide or anti-CD3 Ab. Suboptimal TCR stimulation by plate-bound Ab found to mimic effect APC, indicating...
IL-17-producing CD4+ T helper 17 (Th17) cells are pathogenic in a range of human autoimmune diseases and corresponding animal models. We now demonstrate that such infiltrating the target organ during induction experimental encephalomyelitis (EAE) uveoretinitis (EAU) specifically express NR4A2. Further, we reveal critical involvement NR4A2 Th17 cell functions cell-driven diseases. When expression was blocked with siRNA, full differentiation prevented vitro: although expressed master...
Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported plasmablasts are increased the peripheral blood this autoimmune disease, capable producing 4. Here, we demonstrate CD138+HLA-DR+ plasmablasts, subset IgG-producing cells, enriched among cerebrospinal fluid (CSF)...
Abstract Ghrelin is a recently identified gastric hormone that displays strong growth hormone-releasing activity mediated by the secretagogue receptor. While this unique endogenous peptide participates in regulation of energy homeostasis, increases food intake, and decreases expenditure, its ability to inhibit production proinflammatory cytokines vitro indicates role inflammatory process vivo. Here we examine effect exogenous ghrelin on development experimental autoimmune encephalomyelitis...
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) mediated by Th17 and Th1 cells. DNA microarray analysis previously showed that NR4A2, orphan nuclear receptor, strongly up-regulated in peripheral blood T cells MS. Here, we report NR4A2 plays a pivotal role for mediating cytokine production from pathogenic In experimental encephalomyelitis (EAE), animal model MS, was selectively isolated CNS. Strikingly, forced expression augmented promoter activities IL-17...
Abstract Prior studies have revealed that the sympathetic nervous system regulates clinical and pathological manifestations of experimental autoimmune encephalomyelitis (EAE), an disease model mediated by Th1 T cells. Although regulatory role catecholamines has been indicated in previous works, it remained possible other neurotransmitters like neuropeptide Y (NPY) may also be involved regulation EAE. Here we examined effect NPY receptor subtype-specific compounds on EAE, actively induced...
To examine the physiologic role of natural killer T (NKT) cells bearing V(alpha)14 cell receptor (TCR) in pathogenesis collagen-induced arthritis (CIA) and antibody-induced mice.NKT were stained with alpha-galactosylceramide-loaded CD1 dimer, then assessed using flow cytometry. CIA was induced mice by immunization on days 0 21 type II collagen (CII) emulsified an equal volume Freund's complete adjuvant. Anti-CII antibodies measured enzyme-linked immunosorbent assay. For arthritis, injected...
The altered glycolipid ligand OCH is a selective inducer of Th2 cytokines from NKT cells and potent therapeutic reagent for Th1-mediated autoimmune diseases. Although we have previously shown the intrinsic molecular mechanism preferential IL-4 production by OCH-stimulated cells, little known about extrinsic regulatory network IFN-γ production. Here demonstrate that induces lower IFN-γ, not only but also NK compared with α-galactosylceramide. induced IL-12 due to ineffective primary CD40...
Eomesodermin‐expressing (Eomes + ) T‐helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes Th cell frequency was increased the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by from such patients high compared with controls. A observed initial (acutely progressive) stage sclerosis, a positive correlation between cognitive decline Therefore, may be involved...
To determine whether antilymphocyte Abs to T cell costimulatory molecules are generated in patients with autoimmune diseases and, if they exist, clarify the mechanism of their production and pathological roles, we investigated presence autoantibodies CTLA-4 (CD152), CD28, B7-1 (CD80), B7-2 (CD86) serum samples obtained from various normal subjects using recombinant fusion proteins. In ELISAs, anti-CD28, anti-B7-1, anti-B7-2 were rarely seen, whereas anti-CTLA-4 detected 8.2% systemic lupus...
Significance We have previously demonstrated that induction of pathogenic eomesodermin-positive CD4 + T cells (Eomes helper [Th] cells) is associated with transition from an acute stage to a later experimental autoimmune encephalomyelitis (EAE). In the late phase EAE, B and non-B cell antigen-presenting (APCs) recruited central nervous system strikingly up-regulate prolactin (PRL). The PRL-producing APCs potential promote generation Eomes Th naïve in MHC class II-restricted manner, therapies...
Abstract Objective Stimulation of invariant natural killer T (iNKT) cells with SGL‐S23, a novel synthetic glycolipid analog α‐galactosylceramide an elongated sphingosine chain, has been shown to strongly suppress K/BxN serum transfer arthritis. This study was designed evaluate the protective effects SGL‐S23 in effector phase Methods To induce arthritis, C57BL/6 mice were injected 150 μl from (KRN TCR–transgenic crossed nonobese diabetic mice). Subsequently, ligands administered...
Cancer‑associated fibroblasts (CAFs) in the tumor microenvironment play an essential role progression of esophageal squamous cell carcinoma (ESCC). The present study aimed to investigate expression CAF‑related molecules, versican, periostin and lumican, cancer stroma, provide prognostic stratification for patients with ESCC after surgery. A total 106 who underwent curative esophagectomy without preoperative chemotherapy or radiotherapy were enrolled. stromal proteins, including was examined...
Neurodegeneration is a process involving both cell autonomous and non-cell neuron loss, followed by collapse of neural networks, but its pathogenesis poorly understood. We have previously demonstrated that Eomes-positive helper T (Eomes + Th) cells recognizing LINE-1(L1)-derived prototypic antigen ORF1 mediate neurotoxicity associated with the neurodegenerative pathology experimental autoimmune encephalomyelitis (EAE). Here, we show Eomes Th accumulate in CNS mouse models authentic diseases,...
Fluorescent reporter mouse lines and Cre/Flp recombinase driver play essential roles in investigating various molecular functions vivo. Now that applications of the CRISPR/Cas9 genome-editing system to fertilized eggs have drastically accelerated these knock-in generations, next need is establish easier, quicker, cheaper methods for donor preparation. Here, we reverify optimize phospho-PCR method obtain highly pure long single-stranded DNAs (ssDNAs) suitable generation via genome editing....
CD28 engagement by specific monoclonal antibody (mAb) or binding of the natural ligands, CD80 and CD86, induces tyrosine phosphorylation CD28, which in turn recruits activates signal transducer activator transcription 6 (Stat6). The Stat6 association with is specifically induced CD86 ligand not dependent upon secretion IL-4 IL-13. Activated translocates to nucleus binds a Stat6-responsive element on human promoter. ligation Stat6-dependent transcriptional activation reporter gene under...