CVClient

村上 祐輔

ムラカミ ユウスケ  (Yusuke Murakami)

基本情報

所属
武蔵野大学 薬学部 薬学科 講師
東京大学医科学研究所 共同研究拠点研究員、感染遺伝学分野客員研究員
学位
博士(医学)(東京大学)

研究者番号
50757325
J-GLOBAL ID
201701002243564054
researchmap会員ID
B000273367

論文

 25
  • Kensuke Miyake, Takuma Shibata, Ryutaro Fukui, Yusuke Murakami, Ryota Sato, Ryosuke Hiranuma
    Advances in experimental medicine and biology 1444 97-108 2024年  
    Nucleic acid (NA)-sensing Toll-like receptors (TLRs) reside in the endosomal compartment of innate immune cells, such as macrophages and dendritic cells. NAs transported to the endosomal compartment are degraded by DNases and RNases. Degradation products, including single-stranded DNA, oligoRNA, and nucleosides, are recognized by TLR7, TLR8, and TLR9 to drive the defense responses against pathogens. NA degradation influences endosomal TLR responses by generating and degrading TLR ligands. TLR ligand accumulation because of impaired NA degradation causes constitutive TLR activation, leading to autoinflammatory and autoimmune diseases. Furthermore, some genes associated with these diseases promote endosomal TLR responses. Therefore, endosomal TLRs are promising therapeutic targets for TLR-mediated inflammatory diseases, and novel drugs targeting TLRs are being developed.
  • Tomoya Narita, Yusuke Murakami, Takashi Isii, Masashi Muroi, Naomi Yamashita
    Journal of Leukocyte Biology 2023年12月30日  
    Abstract Eosinophils are typical effector cells associated with type 2 immune responses and play key roles in the pathogenesis of allergic diseases. These cells are activated by various stimuli, such as cytokines, chemokines, and growth factors, but the regulatory mechanisms of eosinophil effector functions remain unclear. Glucocorticoid-induced TNF receptor family-related protein (GITR), a transmembrane protein belonging to the TNF receptor superfamily, is a well-known regulatory molecule for T cell activation. Here, we show that GITR is also constitutively expressed on eosinophils and functions as a co-stimulatory molecule for these cells. Although degranulation was unaffected by GITR engagement of murine bone marrow-derived eosinophils (bmEos), secretion of inflammatory cytokines such as interleukin (IL)-4, IL-6, and IL-13 from IL-33-activated bmEos were augmented by anti-mouse GITR agonistic antibody (DTA-1). In conclusion, our results provide a new regulatory pathway of cytokine secretion from eosinophils where GITR functions as a co-stimulatory molecule.
  • Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro
    Nature communications 14(1) 7349-7349 2023年11月14日  
    Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.
  • Kensuke Miyake, Takuma Shibata, Ryutaro Fukui, Ryota Sato, Shin-Ichiroh Saitoh, Yusuke Murakami
    Frontiers in immunology 13 941931-941931 2022年  
    Toll-like receptors (TLRs) respond to pathogen constituents, such as microbial lipids and nucleic acids (NAs). TLRs recognize NAs in endosomal compartments. Structural and functional studies have shown that recognition of NAs by TLRs depends on NA processing by RNases and DNases. DNase II-dependent DNA degradation is required for TLR9 responses to single-stranded DNAs, whereas RNase T2-dependent RNA degradation enables TLR7 and TLR8 to respond to nucleosides and oligoribonucleotides. In contrast, RNases and DNases negatively regulate TLR responses by degrading their ligands. RNase T2 negatively regulates TLR3 responses to degrading the TLR3 ligand double-stranded RNAs. Therefore, NA metabolism in the endosomal compartments affects the endosomal TLR responses. Dysregulation of NA metabolism in the endosomal compartment drives the TLR-dependent pathologies in human diseases.
  • Am, a L. Gavin, Deli Huang, Tanya R. Blane, Therese C. Thinnes, Yusuke Murakami, Ryutaro Fukui, Kensuke Miyake, David Nemazee
    Nature Communications 12(1) 5874-5874 2021年12月  
    <jats:title>Abstract</jats:title><jats:p>Phospholipase D3 (PLD3) and PLD4 polymorphisms have been associated with several important inflammatory diseases. Here, we show that PLD3 and PLD4 digest ssRNA in addition to ssDNA as reported previously. Moreover, <jats:italic>Pld3</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Pld4</jats:italic><jats:sup>−/−</jats:sup> mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ. Pathology is rescued in <jats:italic>Unc93b1</jats:italic><jats:sup>3d/3d</jats:sup><jats:italic>Pld3</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Pld4</jats:italic><jats:sup>−/−</jats:sup> mice, which lack all endosomal TLR signaling; genetic codeficiency or antibody blockade of TLR9 or TLR7 ameliorates disease less effectively, suggesting that both RNA and DNA sensing by TLRs contributes to inflammation. IFN-γ made a minor contribution to pathology. Elevated type I IFN and some other remaining perturbations in <jats:italic>Unc93b1</jats:italic><jats:sup>3d/3d</jats:sup><jats:italic>Pld3</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Pld4</jats:italic><jats:sup>−/−</jats:sup> mice requires STING (<jats:italic>Tmem173</jats:italic>). Our results show that PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING nucleic acid sensing pathways and have implications for the treatment of nucleic acid-driven inflammatory disease.</jats:p>

MISC

 29

書籍等出版物

 4

担当経験のある科目(授業)

 7

共同研究・競争的資金等の研究課題

 6

産業財産権

 4

教育内容やその他の工夫

 2
  • 件名
    病態学2
    概要
    疾患の炎症部位(組織、臓器)の解剖学から、原因、症状、病態生理、治療方法、予防について系統的に学習する。
  • 件名
    薬物療法学実習
    概要
    講義に準じた疾患の病理学を中心に、フローサイトメーター解析、尿検査などの検査方法も実施する。

教育上の能力に関する大学等の評価

 1
  • 件名
    D合

資格・免許

 1
  • 件名
    獣医師免許