A5091487209- Immune Cell Function and Interaction
- Nuclear Receptors and Signaling
- T-cell and B-cell Immunology
- Macrophage Migration Inhibitory Factor
- Immunotherapy and Immune Responses
- Adenosine and Purinergic Signaling
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- NF-κB Signaling Pathways
- CAR-T cell therapy research
- Inflammasome and immune disorders
- Epigenetics and DNA Methylation
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Pediatric health and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Effects of Radiation Exposure
- Dermatology and Skin Diseases
- Digestive system and related health
- Cardiac Fibrosis and Remodeling
- Autoimmune and Inflammatory Disorders Research
Chiba University
2023-2024
Keio University
2016-2022
National Institute of Dental and Craniofacial Research
2012-2022
National Institutes of Health
2013-2022
Tokyo University of Science
2007-2017
Abstract Psoriasis is an inflammatory skin disease affecting ∼2% of the world’s population, but aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate development autoimmune diseases, their influence on psoriasis We show here that adult mice treated with antibiotics target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, decreased pro-inflammatory IL-17- IL-22-producing T cells....
Epigenome editing is expected to manipulate transcription and cell fates elucidate the gene expression mechanisms in various types. For functional epigenome editing, assessing chromatin context-dependent activity of artificial epigenetic modifier required. In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based mouse primary T cells, focusing on Forkhead box P3 (Foxp3) locus, a master factor regulatory cells (Tregs). The Foxp3 locus regulated...
Abstract Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T SCM ) cells have been proposed as class of long-lived and highly proliferative cells. CD8 + can be generated in vitro from naive via Wnt signalling; however, methods do not yet exist for inducing activated or Here, we show strategy generating -like (iT cells) CD4 mice humans by coculturing with stromal that express Notch ligand. iT lose PD-1 CTLA-4 expression, produce large number...
Antigen-specific regulatory T cells induced in vivo have therapeutic effects mice with established autoimmune diseases.
Abstract Enhanced infiltration of regulatory T cells (Treg) into tumor tissue is detrimental to patients with cancer and closely associated poor prognosis as they create an immunosuppressive state that suppresses antitumor immune responses. Therefore, breaking Treg-mediated tolerance important when considering immunotherapy. Here, we show the Nr4a nuclear receptors, key transcription factors maintaining Treg genetic programs, contribute suppression immunity in microenvironment. Mice lacking...
Abstract Since induced regulatory T cells (iTregs) can be produced in a large quantity vitro, these are expected to clinically useful induce immunological tolerance various diseases. Foxp3 (Forkhead box P3) expression iTregs is, however, unstable due the lack of demethylation CpG island conserved non-coding sequence 2 (CNS2) locus. To facilitate CNS2, we over-expressed catalytic domain (CD) ten-eleven translocation (TET) protein, which catalyzes steps iterative 5-methylcytosine. TET-CD...
We recently reported that repeated 0.5-Gy gamma irradiation attenuates the pathology of collagen-induced arthritis. In this study, to investigate mechanism further, we focused on changes in Treg/Th17 cells and production antibody against an external antigen response as well radiosensitivity Treg cells. DBA/1J mice were immunized with type II collagen induce arthritis exposed low-dose rays (0.5 Gy/week for 5 weeks). Production IL6 IL17 autoantibody was suppressed by early phase The percentage...
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Although vitro-expanded antigen-specific induced Tregs (iTregs) have been considered be a promising therapeutic agent against such excessive reactions, instability of iTregs transfer is fundamental problem their clinical application. In...
Ten-eleven translocation (TET) proteins regulate DNA methylation and gene expression by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Although Tet2/Tet3 deficiency has been reported lead myeloid cell, B-cell invariant natural killer T (iNKT) cell malignancy, the effect of TET on regulatory cells (Tregs) not elucidated. We found that in Tregs led lethal hyperproliferation CD4+Foxp3+ spleen mesenteric lymph nodes after 5 months age. Additionally, aged Treg-specific...
We previously reported attenuation of autoimmune disease by low-dose gamma-ray irradiation in MRL-lpr/lpr mice. Here, we studied the effect on collagen-induced arthritis (CIA) DBA/1J Mice were immunized with type II collagen, and exposed to gamma-rays (0.5 Gy per week for 5 weeks). Paw swelling, redness, bone degradation suppressed irradiation, which also delayed onset pathological change reduced severity arthritis. Production tumor necrosis factor-alpha, interferon-gamma, interleukin-6,...
Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced that serve mitigate or repair injurious effects γ on body. Indeed, low doses may have net beneficial effect by activating protective mechanisms, including antitumor immune responses. On other hand, ATP be involved resistance cancer cells. Here, focusing our previous work, we review evidence low-dose irradiation...
We previously showed that regulatory T cells (Tregs) from cell-specific Socs1-deficient mice (Socs1fl/flLck-Cre+ mice) easily convert into Th1- or Th17-like (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs Socs1fl/flLck-Cre+ are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs vivo, this study we analyzed Treg-specific (Socs1fl/flFoxp3YFP-Cre mice). These developed dermatitis, splenomegaly, lymphadenopathy were much...
Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the remodeling that occurs response pressure overload. However, possible of T cells this process, not well characterized. Here we show cell depletion conferred late-stage heart protection but induced cardioprotective hypertrophy at an early stage caused Single-cell RNA sequencing analysis revealed CD8 + with...
Abstract Interleukin-9 (IL-9)-producing CD4 + T helper cells (Th9) have been implicated in allergy/asthma and anti-tumor immunity, yet molecular insights on their differentiation from activated cells, driven by IL-4 transforming growth factor-beta (TGF-β), is still lacking. Here we show opposing functions of two transcription factors, D-binding protein (DBP) E2F8, controlling Th9 differentiation. Specifically, TGF-β signaling induces phosphorylation the serine 213 site linker region Smad3...
We recently reported attenuation of autoimmune disease by low-dose gamma irradiation (repeated doses 0.5 Gy) in MRL-lpr/ lpr mice. Here we studied the effect on experimental encephalomyelitis (EAE), which is a rodent model multiple sclerosis. SJL/J mice were immunized with myelin basic protein for induction EAE and exposed to Gy rays once week 4 weeks. Radiation suppressed incidence severity scores delayed onset pathological changes. Pro-inflammatory cytokines (IFN-gamma IL6), autoantibody...
Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation Foxp3 + Tregs from naïve CD4 local tumor microenvironment. TGF-β activates nuclear kappa B (NF-κB)/p300 and SMAD signaling, increases number acetylated histones at locus induces gene expression. also helps stabilize The curcumin analog agent, GO-Y030, prevented TGF-β-induced by...