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Teruhito Yasui
| Institute for Genetic Medicine Molecular Pathogenesis | Postdoctoral Fellow |
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■ Papers- Development of a recombinant hepatitis B immunoglobulin derived from B cells collected from healthy individuals administered with hepatitis B virus vaccines: A feasibility study
Rika A. Furuta; Teruhito Yasui; Takeharu Minamitani; Hiroki Akiba; Chizu Toyoda; Ryutaro Tobita; Kazuta Yasui; Ryota Aminaka; Mikako Masaki; Masahiro Satake
Transfusion, 63, 6, 1204, 1214, Wiley, 29 Apr. 2023
Scientific journal - Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein
Ryota Otsubo; Takeharu Minamitani; Kouji Kobiyama; Junso Fujita; Toshihiro Ito; Shiori Ueno; Itsuki Anzai; Hiroki Tanino; Hiroshi Aoyama; Yoshiharu Matsuura; Keiichi Namba; Ken-Ichi Imadome; Ken J. Ishii; Kouhei Tsumoto; Wataru Kamitani; Teruhito Yasui
Scientific Reports, 12, 1, 20120, 20120, Springer Science and Business Media LLC, 22 Nov. 2022, [International Magazine]
English, Scientific journal, Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs. - Food odor perception promotes systemic lipid utilization
Hiroshi Tsuneki; Masanori Sugiyama; Toshihiro Ito; Kiyofumi Sato; Hiroki Matsuda; Kengo Onishi; Koharu Yubune; Yukina Matsuoka; Sanaka Nagai; Towa Yamagishi; Takahiro Maeda; Kosuke Honda; Akira Okekawa; Shiro Watanabe; Keisuke Yaku; Daisuke Okuzaki; Ryota Otsubo; Masanori Nomoto; Kaoru Inokuchi; Takashi Nakagawa; Tsutomu Wada; Teruhito Yasui; Toshiyasu Sasaoka
Nature Metabolism, 4, 1514, 1531, Springer Science and Business Media LLC, 14 Nov. 2022
Scientific journal - ヒト抗破傷風毒素中和抗体開発とその作用機序
大坪 亮太; 伊藤 寿宏; 安居 輝人
日本細菌学雑誌, 77, 1, 103, 103, 日本細菌学会, Feb. 2022
Japanese - Monoclonal antibody therapeutics for infectious diseases: Beyond normal human immunoglobulin
Ryota Otsubo; Teruhito Yasui
Pharmacology and Therapeutics, 240, 108233, 108233, 108233, 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Antibody therapy is effective for treating infectious diseases. Due to the coronavirus disease 2019 (COVID-19) pandemic and the rise of drug-resistant bacteria, rapid development of neutralizing monoclonal antibodies (mAbs) to treat infectious diseases is urgently needed. Using a therapeutic human mAb with the lowest immunogenicity is recommended, because chimera and humanized mAbs are occasionally immunogenic. In order to directly obtain naïve human mAbs, there are three methods: phage display, B cell receptor (BCR) cDNA sequencing of a single cell, and antibody-encoding gene and amino acid sequencing of immortalized cells using memory B cells, which are isolated from human peripheral blood mononuclear cells of healthy, vaccinated, infected, or recovered individuals. After screening against the antigen and performing neutralization assays, a human neutralizing mAb is constructed from the antibody-encoding DNA sequences of these memory B cells. This review describes examples of obtaining human neutralizing mAbs against various infectious diseases using these methods. However, a few of these mAbs have been approved for therapy. Therefore, antigen characterization and evaluation of neutralization activity in vitro and in vivo are indispensable for the development of therapeutic mAbs. These results will accelerate the development of antibody drug as therapeutic agents. - Optimization of anti-ADAMTS13 antibodies for the treatment of ADAMTS13-related bleeding disorder in patients receiving circulatory assist device support
Toshihiro Ito; Takeharu Minamitani; Masaki Hayakawa; Ryota Otsubo; Hiroki Akiba; Kouhei Tsumoto; Masanori Matsumoto; Teruhito Yasui
Scientific Reports, 11, 22341, 22341, 22341, Springer Science and Business Media LLC, Dec. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Abstract
ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motif 13)-related bleeding disorder has been frequently observed as a life-threatening clinical complication in patients carrying a circulatory assist device. Currently, treatment modalities for the bleeding disorder are very limited and not always successful. To address the unmet medical need, we constructed humanized antibodies of mouse anti-ADAMTS13 antibody A10 (mA10) by using complementarity-determining region (CDR) grafting techniques with human antibody frameworks, 8A7 and 16E8. The characteristics of the two humanized A10 antibodies, namely A10/8A7 and A10/16E8, were assessed in vitro and in silico. Among the two humanized A10 antibodies, the binding affinity of A10/16E8 to ADAMTS13 was comparable to that of mA10 and human-mouse chimeric A10. In addition, A10/16E8 largely inhibited the ADAMTS13 activity in vitro. The results indicated that A10/16E8 retained the binding affinity and inhibitory activity of mA10. To compare the antibody structures, we performed antibody structure modeling and structural similarity analysis in silico. As a result, A10/16E8 showed higher structural similarity to mA10, compared with A10/8A7, suggesting that A10/16E8 retains a native structure of mA10 as well as its antigen binding affinity and activity. A10/16E8 has great potential as a therapeutic agent for ADAMTS13-related bleeding disorder. - Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
Takeharu Minamitani; Karin Kiyose; Ryota Otsubo; Toshihiro Ito; Hiroki Akiba; Rika A. Furuta; Tsuyoshi Inoue; Kouhei Tsumoto; Masahiro Satake; Teruhito Yasui
Scientific Reports, 11, 12134, 12134, 12134, 09 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)-reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix-reactive antibodies provided enhanced protection compared to the use of each antibody alone. - Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway
Mizuki Watanabe; Jun Arii; Kosuke Takeshima; Ayano Fukui; Masayuki Shimojima; Hiroko Kozuka-Hata; Masaaki Oyama; Takeharu Minamitani; Teruhito Yasui; Yuji Kubota; Mutsuhiro Takekawa; Isao Kosugi; Yuhei Maruzuru; Naoto Koyanagi; Akihisa Kato; Yasuko Mori; Yasushi Kawaguchi
Journal of Virology, 95, 3, American Society for Microbiology, 11 Nov. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal,ABSTRACT
Viral cell-to-cell spread, a method employed by several viral families for entrance via cell junctions, is highly relevant to the pathogenesis of various viral infections. Cell-to-cell spread of herpes simplex virus 1 (HSV-1) is known to depend greatly on envelope glycoprotein E (gE). However, the molecular mechanism by which gE acts in HSV-1 cell-to-cell spread and the mechanisms of cell-to-cell spread by other herpesviruses remain poorly understood. Here, we describe our identification of prohibitin-1 as a novel gE-interacting host cell protein. Ectopic expression of prohibitin-1 increased gE-dependent HSV-1 cell-to-cell spread. As observed with the gE-null mutation, decreased expression or pharmacological inhibition of prohibitin-1 reduced HSV-1 cell-to-cell spread without affecting the yield of virus progeny. Similar effects were produced by pharmacological inhibition of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, wherein prohibitin-1 acts as a protein scaffold and is required for induction of this pathway. Furthermore, artificial activation of the MAPK/ERK pathway restored HSV-1 cell-to-cell spread impaired by the gE-null mutation. Notably, pharmacological inhibition of prohibitins or the MAPK/ERK pathway reduced viral cell-to-cell spread of representative members in all herpesvirus subfamilies. Our results suggest that prohibitin-1 contributes to gE-dependent HSV-1 cell-to-cell spread via the MAPK/ERK pathway and that this mechanism is conserved throughout theHerpesviridae , whereas gE is conserved only in theAlphaherpesvirinae subfamily.IMPORTANCE Herpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells. This method of cell-to-cell spread is an important pathogenic characteristic of these viruses. Here, we show that the host cell protein prohibitin-1 contributes to HSV-1 cell-to-cell spread via a downstream intracellular signaling cascade, the MAPK/ERK pathway. We also demonstrate that the role of the prohibitin-1-mediated MAPK/ERK pathway in viral cell-to-cell spread is conserved in representative members of every herpesvirus subfamily. This study has revealed a common molecular mechanism of the cell-to-cell spread of herpesviruses. - The Kg‐antigen, RhAG with a Lys164Gln mutation, gives rise to haemolytic disease of the newborn
Mitsunobu Tanaka; Takaaki Abe; Takeharu Minamitani; Hiroki Akiba; Toshihiro Horikawa; Ryutaro Tobita; Kazumi Isa; Kenichi Ogasawara; Hideo Takahashi; Hidemi Tateyama; Satomi Tone; Kouhei Tsumoto; Teruhito Yasui; Takafumi Kimura; Yoshihiro Fujimura; Fumiya Hirayama; Yoshihiko Tani; Yoshihiro Takihara
British Journal of Haematology, 191, 5, 920, 926, Wiley, 23 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The Kg-antigen was first discovered in an investigation of a mother whose infant had haemolytic disease of the newborn (HDN). The antibody against the Kg-antigen is believed to be responsible for HDN. The Kg-antigen is provisionally registered under the number 700045, according to the Red Cell Immunogenetics and Blood Group Terminology. However, the molecular nature of the Kg-antigen has remained a mystery for over 30 years. In this study, a monoclonal antibody against the Kg-antigen and the recombinant protein were developed that allowed for the immunoprecipitation analysis. Immunoprecipitants from the propositus' red blood cell ghosts were subjected to mass spectrometry analysis, and DNA sequence analysis of the genes was also performed. A candidate for the Kg-antigen was molecularly isolated and confirmed to be a determinant of the Kg-antigen by cell transfection and flow cytometry analyses. The Kg-antigen and the genetic mutation were then screened for in a Japanese population. The molecular nature of the Kg-antigen was shown to be RhAG with a Lys164Gln mutation. Kg phenotyping further clarified that 0.22% of the Japanese population studied was positive for the Kg-antigen. These findings provide important information on the Kg-antigen, which has been clinically presumed to give rise to HDN. - Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction–Mediated Cell-Cell Interaction
Akie Kikuchi-Taura; Yuka Okinaka; Yukiko Takeuchi; Yuko Ogawa; Mitsuyo Maeda; Yosky Kataoka; Teruhito Yasui; Takafumi Kimura; Sheraz Gul; Carsten Claussen; Johannes Boltze; Akihiko Taguchi
Stroke, 51, 4, 1279, 1289, Ovid Technologies (Wolters Kluwer Health), 19 Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal,
Background and Purpose—
Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis.
Methods—
We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue.
Results—
The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed.
Conclusions—
Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy.
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- Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection
Shuhei Sakakibara; Teruhito Yasui; Hideyuki Jinzai; Kristy O’Donnell; Chao-Yuan Tsai; Takeharu Minamitani; Kazuya Takeda; Gabrielle T Belz; David M Tarlinton; Hitoshi Kikutani
International Immunology, 32, 1, 27, 38, Oxford University Press (OUP), 09 Jan. 2020, [Peer-reviewed]
Scientific journal,Abstract
Immune responses against certain viruses are accompanied by auto-antibody production although the origin of these infection-associated auto-antibodies is unclear. Here, we report that murine γ-herpesvirus 68 (MHV68)-induced auto-antibodies are derived from polyreactive B cells in the germinal center (GC) through the activity of short-lived plasmablasts. The analysis of recombinant antibodies from MHV68-infected mice revealed that about 40% of IgG+ GC B cells were self-reactive, with about half of them being polyreactive. On the other hand, virion-reactive clones accounted for only a minor proportion of IgG+ GC B cells, half of which also reacted with self-antigens. The self-reactivity of most polyreactive clones was dependent on somatic hypermutation (SHM), but this was dispensable for the reactivity of virus mono-specific clones. Furthermore, both virus-mono-specific and polyreactive clones were selected to differentiate to B220lo CD138+ plasma cells (PCs). However, the representation of GC-derived polyreactive clones was reduced and that of virus-mono-specific clones was markedly increased in terminally differentiated PCs as compared to transient plasmablasts. Collectively, our findings demonstrate that, during acute MHV68 infection, self-reactive B cells are generated through SHM and selected for further differentiation to short-lived plasmablasts but not terminally differentiated PCs. - Bystander inhibition of humoral immune responses by Epstein-Barr virus LMP1
Tsai CY; Sakakibara S; Yasui T; Minamitani T; Okuzaki D; Kikutani H
International Immunology, 30, 12, 579, 590, Oxford Academic, Dec. 2018, [Peer-reviewed]
English, Scientific journal - Bystander inhibition of humoral immune responses by Epstein-Barr virus LMP1
Chao Yuan Tsai; Shuhei Sakakibara; Teruhito Yasui; Takeharu Minamitani; Daisuke Okuzaki; Hitoshi Kikutani
International immunology, 30, 12, 579, 590, 14 Nov. 2018, [Peer-reviewed]
English, Scientific journal - Murine g-herpesvirus 68 induces severe lung inflammation in IL-27–deficient mice with liver dysfunction preventable by oral neomycin
Kyosuke Kanai; Ah-Mee Park; Akiko Watanabe; Tomohiro Arikawa; Teruhito Yasui; Hiroki Yoshida; Ikuo Tsunoda; Osamu Yoshie
Journal of Immunology, 200, 8, 2703, 2713, American Association of Immunologists, 15 Apr. 2018, [Peer-reviewed]
English, Scientific journal - Autoimmune diseases and EB virus LMP2A
Takeharu MINAMITANI; Teruhito YASUI
Clinical immunology & allergology, 68, 3, 334, 340, 科学評論社, Sep. 2017
Japanese, Scientific journal - Mouse model of Epstein–Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease
Takeharu Minamitani; Yijie Ma; Hufeng Zhou; Hiroshi Kida; Chao-Yuan Tsai; Masanori Obana; Daisuke Okuzaki; Yasushi Fujio; Atsushi Kumanogoh; Bo Zhao; Hitoshi Kikutani; Elliott Kieff; Benjamin E. Gewurz; Teruhito Yasui
Proceedings of the National Academy of Sciences, 114, 18, 4751, 4756, 02 May 2017, [Peer-reviewed]
Scientific journal - Chronic inflammation and virus persistent infection
Teruhito YASUI
The Medical Frontline, 71, 11, 2344, 2350, Nov. 2016
Japanese, Scientific journal - The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation
Yusuke Yamazumi; Oh Sasaki; Mitsuru Imamura; Takeaki Oda; Yoko Ohno; Yumi Shiozaki-Sato; Shigenori Nagai; Saki Suyama; Yuki Kamoshida; Kosuke Funato; Teruhito Yasui; Hitoshi Kikutani; Kazuhiko Yamamoto; Makoto Dohi; Shigeo Koyasu; Tetsu Akiyama
Cell Reports, 16, 9, 2456, 2471, Aug. 2016, [Peer-reviewed]
Scientific journal - Caspase-dependent cleavage regulates protein levels of Epstein-Barr virus-derived latent membrane protein 1
Sumihito Togi; Yosuke Hatano; Ryuta Muromoto; Eri Kawanishi; Osamu Ikeda; Koki Hirashima; Shigeyuki Kon; Yuichi Kitai; Teruhito Yasui; Kenji Oritani; Tadashi Matsuda
FEBS LETTERS, 590, 6, 808, 818, Mar. 2016, [Peer-reviewed]
English, Scientific journal - Evasion of affinity-based selection in germinal centers by Epstein-Barr virus LMP2A
Takeharu Minamitani; Teruhito Yasui; Yijie Ma; Hufeng Zhou; Daisuke Okuzaki; Chiau-Yuang Tsai; Shuhei Sakakibara; Benjamin E. Gewurz; Elliott Kieff; Hitoshi Kikutani
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112, 37, 11612, 11617, Sep. 2015, [Peer-reviewed]
English, Scientific journal - B細胞におけるPKCの生理機能と分子機序
YASUI Teruhito; MINAMITANI Takeharu
Inflammation & Immunity, 23, 5, 450, 454, Sep. 2015
Japanese, Scientific journal - Partial suppression of M1 microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosis
Satoru Tada; Tatsusada Okuno; Yasumichi Hitoshi; Teruhito Yasui; Josephe Archie Honorat; Kazushiro Takata; Toru Koda; Hiroshi Shimagami; Choong Chi-Jing; Akiko Namba; Tomoyuki Sugimoto; Saburo Sakoda; Hideki Mochizuki; Hitoshi Kikutani; Yuji Nakatsuji
JOURNAL OF NEUROINFLAMMATION, 11, 179, 186, Oct. 2014, [Peer-reviewed]
English, Scientific journal - Significance of Glycosylphosphatidylinositol-anchored Protein Enrichment in Lipid Rafts for the Control of Autoimmunity
Yetao Wang; Yoshiko Murakami; Teruhito Yasui; Shigeharu Wakana; Hitoshi Kikutani; Taroh Kinoshita; Yusuke Maeda
JOURNAL OF BIOLOGICAL CHEMISTRY, 288, 35, 25490, 25499, Aug. 2013, [Peer-reviewed]
English, Scientific journal - BCR signal strength required for affinity maturation of germinal center B cells
Takeharu MINAMITANI; Hitoshi KIKUTANI; Teruhito YASUI
Clinical immunology & allergology, 60, 2, 109, 114, Aug. 2013
Japanese, Scientific journal - BAFF Controls Neural Cell Survival through BAFF Receptor
Satoru Tada; Teruhito Yasui; Yuji Nakatsuji; Tatsusada Okuno; Toru Koda; Hideki Mochizuki; Saburo Sakoda; Hitoshi Kikutani
PLOS ONE, 8, 7, e70924, Jul. 2013, [Peer-reviewed]
English, Scientific journal - An Inhibitory Role for Sema4A in Antigen-Specific Allergic Asthma
Tetsuo Morihana; Sho Goya; Masayuki Mizui; Teruhito Yasui; Durubaka V. R. Prasad; Atsushi Kumanogoh; Manabu Tamura; Takashi Shikina; Yohei Maeda; Yoriko Iwamoto; Hidenori Inohara; Hitoshi Kikutani
JOURNAL OF CLINICAL IMMUNOLOGY, 33, 1, 200, 209, Jan. 2013, [Peer-reviewed]
English, Scientific journal - Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation
T. Yasui; K. Sakakibara-Yada; T. Nishimura; K. Morita; S. Tada; G. Mosialos; E. Kieff; H. Kikutani
Proceedings of the National Academy of Sciences, 109, 51, 21022, 21027, 18 Dec. 2012
Scientific journal - Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohnʼs disease
Takahiro Inoue; Hideki Iijima; Michiko Tajiri; Shinichiro Shinzaki; Eri Shiraishi; Satoshi Hiyama; Akira Mukai; Sachiko Nakajima; Hirotsugu Iwatani; Tsutomu Nishida; Tsunekazu Mizushima; Teruhito Yasui; Yoshitaka Isaka; Tatsuya Kanto; Masahiko Tsujii; Eiji Miyoshi; Yoshinao Wada; Tetsuo Takehara
Inflammatory Bowel Diseases, 18, 9, 1723, 1734, Sep. 2012, [Peer-reviewed]
English, Scientific journal - Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor
Chigusa Nakahashi-Oda; Satoko Tahara-Hanaoka; Masamichi Shoji; Yasushi Okoshi; Takako Nakano-Yokomizo; Nobuhiro Ohkohchi; Teruhito Yasui; Hitoshi Kikutani; Shin-ichiro Honda; Kazuko Shibuya; Shigekazu Nagata; Akira Shibuya
JOURNAL OF EXPERIMENTAL MEDICINE, 209, 8, 1493, 1503, Jul. 2012, [Peer-reviewed]
English, Scientific journal - The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses
Takako Nakano-Yokomizo; Satoko Tahara-Hanaoka; Chigusa Nakahashi-Oda; Tsukasa Nabekura; Nadia K. Tchao; Momoko Kadosaki; Naoya Totsuka; Naoki Kurita; Kiyotaka Nakamagoe; Akira Tamaoka; Toshiyuki Takai; Teruhito Yasui; Hitoshi Kikutani; Shin-ichiro Honda; Kazuko Shibuya; Lewis L. Lanier; Akira Shibuya
JOURNAL OF EXPERIMENTAL MEDICINE, 208, 8, 1661, 1671, Aug. 2011, [Peer-reviewed]
English, Scientific journal - Deleterious effects of lymphocytes at the early stage of neurodegeneration in an animal model of amyotrophic lateral sclerosis
Satoru Tada; Tatsusada Okuno; Teruhito Yasui; Yuji Nakatsuji; Tomoyuki Sugimoto; Hitoshi Kikutani; Saburo Sakoda
JOURNAL OF NEUROINFLAMMATION, 8, 23, 19, 28, Feb. 2011, [Peer-reviewed]
English, Scientific journal - Cutting Edge: Critical Role of I kappa B Kinase alpha in TLR7/9-Induced Type I IFN Production by Conventional Dendritic Cells
Katsuaki Hoshino; Izumi Sasaki; Takahiro Sugiyama; Takahiro Yano; Chihiro Yamazaki; Teruhito Yasui; Hitoshi Kikutani; Tsuneyasu Kaisho
JOURNAL OF IMMUNOLOGY, 184, 7, 3341, 3345, Apr. 2010, [Peer-reviewed]
English, Scientific journal - BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappa B activation
Osamu Ikeda; Yuto Miyasaka; Ryuji Yoshida; Akihiro Mizushima; Kenji Oritani; Yuichi Sekine; Makoto Kuroda; Teruhito Yasui; Masahiro Fujimuro; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda
FEBS LETTERS, 584, 5, 865, 872, Mar. 2010, [Peer-reviewed]
English, Scientific journal - Enhanced humoral immune responses against T-independent antigens in Fc alpha/mu R-deficient mice
Shin-ichiro Honda; Naoki Kurita; Akitomo Miyamoto; Yukiko Cho; Kenta Usui; Kie Takeshita; Satoru Takahashi; Teruhito Yasui; Hitoshi Kikutani; Taroh Kinoshita; Teizo Fujita; Satoko Tahara-Hanaoka; Kazuko Shibuya; Akira Shibuya
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106, 27, 11230, 11235, Jul. 2009, [Peer-reviewed]
English, Scientific journal - BS69 negatively regulates the canonical NF-kappa B activation induced by Epstein-Barr virus-derived LMP1
Osamu Ikeda; Yuichi Sekine; Akihiro Mizushima; Kenji Oritani; Teruhito Yasui; Masahiro Fujimuro; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda
FEBS LETTERS, 583, 10, 1567, 1574, May 2009, [Peer-reviewed]
English, Scientific journal - Accelerated tumor growth in mice deficient in DNAM-1 receptor
Akiko Iguchi-Manaka; Hirayasu Kai; Yumi Yamashita; Kai Shibata; Satoko Tahara-Hanaoka; Shin-ichiro Honda; Teruhito Yasui; Hitoshi Kikutani; Kazuko Shibuya; Akira Shibuya
JOURNAL OF EXPERIMENTAL MEDICINE, 205, 13, 2959, 2964, Dec. 2008, [Peer-reviewed]
English, Scientific journal - STAP-2 negatively regulates both canonical and noncanonical NF-kappa B activation induced by Epstein-Barr virus-derived latent membrane protein 1
Osamu Ikeda; Yuichi Sekine; Teruhito Yasui; Kenji Oritani; Kenji Sugiyma; Ryuta Muromoto; Norihiko Ohbayashi; Akihiko Yoshimura; Tadashi Matsuda
MOLECULAR AND CELLULAR BIOLOGY, 28, 16, 5027, 5042, Aug. 2008, [Peer-reviewed]
English, Scientific journal - Bimodal regulation of T cell-mediated immune responses by TIM-4
Masayuki Mizui; Takashi Shikina; Hisashi Arase; Kazuhiro Suzuki; Teruhito Yasui; Paul D. Rennert; Atsushi Kumanogoh; Hitoshi Kikutani
INTERNATIONAL IMMUNOLOGY, 20, 5, 695, 708, May 2008, [Peer-reviewed]
English, Scientific journal - T細胞反応におけるTim-4の二相性作用(Biophasic action of Tim-4 on T cell-mediated immune responses)
Mizui Masayuki; Arase Hisashi; Suzuki Kazuhiro; Yasui Teruhito; Kumanogoh Atsushi; Kikutani Hitoshi
日本免疫学会総会・学術集会記録, 37, 220, 220, (NPO)日本免疫学会, Oct. 2007
English - 樹状細胞の機能 トレランスと機能偏向を中心に ナイーブT細胞活性化におけるTim-4の阻害的役割(An inhibitory role of Tim-4 in naive T-cell activation)
Mizui Masayuki; Arase Hisashi; Morihana Tetsuo; Yasui Teruhito; Kumanogoh Atsushi; Kikutani Hitoshi
日本免疫学会総会・学術集会記録, 36, 214, 214, (NPO)日本免疫学会, Nov. 2006
English - LMP1 transmembrane domain 1 and 2 (TM1-2) FWLY mediates intermolecular interactions with TM3-6 to activate NF-kappa B
Vishal Soni; Teruhito Yasui; Ellen Cahir-McFarland; Elliott Kieff
JOURNAL OF VIROLOGY, 80, 21, 10787, 10793, Nov. 2006, [Peer-reviewed]
English, Scientific journal - Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice
MS Kang; HX Lu; T Yasui; A Sharpe; H Warren; E Cahir-McFarland; R Bronson; SC Hung; E Kieff
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 102, 3, 820, 825, Jan. 2005, [Peer-reviewed]
English, Scientific journal - Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK -dependent noncanonical NF- B activation
M. Luftig; T. Yasui; V. Soni; M.-S. Kang; N. Jacobson; E. Cahir-McFarland; B. Seed; E. Kieff
Proceedings of the National Academy of Sciences, 101, 1, 141, 146, 06 Jan. 2004, [Peer-reviewed]
English, Scientific journal - Latent infection membrane protein transmembrane FWLY is critical for intermolecular interaction, raft localization, and signaling
T Yasui; M Luftig; Soni, V; E Kieff
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101, 1, 278, 283, Jan. 2004, [Peer-reviewed]
English, Scientific journal - Epstein-Barr virus latent membrane protein 1 activation of NF- B through IRAK1 and TRAF6
M. Luftig; E. Prinarakis; T. Yasui; T. Tsichritzis; E. Cahir-McFarland; J.-I. Inoue; H. Nakano; T. W. Mak; W.-C. Yeh; X. Li; S. Akira; N. Suzuki; S. Suzuki; G. Mosialos; E. Kieff
Proceedings of the National Academy of Sciences, 100, 26, 15595, 15600, 23 Dec. 2003, [Peer-reviewed]
English, Scientific journal - Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis
Y Komatsu; H Shibuya; N Takeda; J Ninomiya-Tsuji; T Yasui; K Miyado; T Sekimoto; N Ueno; K Matsumoto; G Yamada
MECHANISMS OF DEVELOPMENT, 119, 2, 239, 249, Dec. 2002, [Peer-reviewed]
English, Scientific journal - Endotoxin can induce MyD88-deficient dendritic cells to support T(h)2 cell differentiation
T Kaisho; K Hoshino; T Iwabe; O Takeuchi; T Yasui; S Akira
INTERNATIONAL IMMUNOLOGY, 14, 7, 695, 700, Jul. 2002, [Peer-reviewed]
English, Scientific journal - Short-circuiting long-lived humoral immunity by the heightened engagement of CD40
LD Erickson; BG Durell; LA Vogel; BP O'Connor; M Cascalho; T Yasui; H Kikutani; RJ Noelle
JOURNAL OF CLINICAL INVESTIGATION, 109, 5, 613, 620, Mar. 2002, [Peer-reviewed]
English, Scientific journal - Dissection of B cell differentiation during primary immune responses in mice with altered CD40 signals
T Yasui; M Muraoka; Y Takaoka-Shichijo; Ishida, I; N Takegahara; J Uchida; A Kumanogoh; S Suematsu; M Suzuki; H Kikutani
INTERNATIONAL IMMUNOLOGY, 14, 3, 319, 329, Mar. 2002, [Peer-reviewed]
English, Scientific journal - Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: A novel mechanism for regulating B cell signaling
A Kumanogoh; C Watanabe; Lee, I; XS Wang; W Shi; H Araki; H Hirata; K Iwahori; J Uchida; T Yasui; M Matsumoto; K Yoshida; H Yakura; C Pan; Parnes, JR; H Kikutani
IMMUNITY, 13, 5, 621, 631, Nov. 2000, [Peer-reviewed]
English, Scientific journal - The class IV semaphorin CD100 plays nonredundant roles in the immune system: Defective B and T cell activation in CD100-deficient mice
W Shi; A Kumanogoh; C Watanabe; J Uchida; XS Wang; T Yasui; K Yukawa; M Ikawa; M Okabe; Parnes, JR; K Yoshida; H Kikutani
IMMUNITY, 13, 5, 633, 642, Nov. 2000, [Peer-reviewed]
English, Scientific journal - Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses
J Uchida; T Yasui; Y Takaoka-Shichijo; M Muraoka; W Kulwichit; N Raab-Traub; H Kikutani
SCIENCE, 286, 5438, 300, 303, Oct. 1999, [Peer-reviewed]
English, Scientific journal - CD40シグナル
Teruhito YASUI; Hitoshi KIKUTANI
遺伝子医学, 3, 109, 114, 1999
Japanese, Scientific journal - Protective effect of Wen-Pi-Tang against apoptosis of cultured renal epithelial cells
Takako Yokozawa; Erbo Dong; Teruto Yasui; Atsushi Muraguchi
Phytotherapy Research, 12, 2, 135, 137, Mar. 1998, [Peer-reviewed]
English, Scientific journal - Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130
A Kumanogoh; S Marukawa; T Kumanogoh; H Hirota; K Yoshida; IS Lee; T Yasui; K Yoshida; T Taga; T Kishimoto
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94, 6, 2478, 2482, Mar. 1997, [Peer-reviewed]
English, Scientific journal - Impairment of antibody production in transgenic mice overexpressing a dominant-negative form of gp130.
Kumanogoh A; Marukawa S; Kumanogoh T; Hirota H; Yoshida K; Lee IS; Yoshida K; Yasui T; Kishimoto T; Taga T.(ed; T. Kishimoto
Leukocyte Typing IV, 888, 889, 1997
English, Scientific journal - Pysiological signaling of CD40 in human CD40-transgenic mice.
Yasui T; Hayami K; Kamanaka M; Kumanogoh A; Uchida J; Suematsu S; Suzuki M; Muraguchi A; Kishimoto T; Kikutani H; ed; T. Kishimoto
Leukocyte Typing IV, 258, 259, 1997
English, Scientific journal - CD40とTRAF
Teruhito YASUI; Hitoshi KIKUTANI
Molecular Medicine, 34, 1997, 98, 104, 中山書店, 1997
Japanese, Scientific journal - Profound reduction of mature B cell numbers, reactivities and serum Ig levels in mice which simultaneously carry the XID and CD40 deficiency genes
Y Oka; AG Rolink; J Andersson; M Kamanaka; J Uchida; T Yasui; T Kishimoto; H Kikutani; F Melchers
INTERNATIONAL IMMUNOLOGY, 8, 11, 1675, 1685, Nov. 1996, [Peer-reviewed]
English, Scientific journal - Molecular biological analysis of the effects of ginsenoside-Rb-2 on albumin mRNA in streptozotocin-induced diabetic rats
T Yokozawa; T Yasui; H Oura
JOURNAL OF PHARMACY AND PHARMACOLOGY, 48, 7, 763, 767, Jul. 1996, [Peer-reviewed]
English, Scientific journal - Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity
M Kamanaka; P Yu; T Yasui; K Yoshida; T Kawabe; T Horii; T Kishimoto; H Kikutani
IMMUNITY, 4, 3, 275, 281, Mar. 1996, [Peer-reviewed]
English, Scientific journal - CD40-CD40L-免疫応答制御におけるシグナル伝達
Teruhito YASUI; Hitoshi KIKUTANI
実験医学増刊「免疫系のシグナル伝達」, 14, 833, 837, 1996
Japanese, Scientific journal - The roles of CD40 and CD23 in IgE regulation
T Yasui; H Fujiwara; M Kamanaka; T Kawabe; N Yoshida; T Kishimoto; H Kikutani
NEW HORIZONS IN ALLERGY IMMUNOTHERAPY, 409, 349, 354, 1996
English, International conference proceedings - Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc-1/skn-1a
K Yukawa; K Butz; T Yasui; H Kikutani; F HoppeSeyler
JOURNAL OF VIROLOGY, 70, 1, 10, 16, Jan. 1996, [Peer-reviewed]
English, Scientific journal - CD40欠損マウスにおける免疫反応
川部勤; 鎌仲正人; 安居輝人; 菊谷仁
Molecular Medicine増刊「免疫1995-1996」, 32, 30, 40, 1995
Japanese, Scientific journal - EBウイルスの形質転換機構 TNFRファミリーとTRAFファミリーに関する話題
Teruhito YASUI; Hitoshi KIKUTANI
細胞工学, 14, 1449, 1454, 1995
Japanese, Scientific journal - Decrease in the level of albumin mRNA with progression of renal failure in rats
Takako Yokozawa; Teruhito Yasui; Sanae Ishii; Hikokichi Oura
The Japanese Journal of Nephrology, 36, 4, 317, 321, 1994
English, Scientific journal - Epoc-1: a POU-domain gene expressed in murine epidermal basal cells and thymic stromal cells
Yukawa K; Yasui T; Yamamoto A; Shiku H; Kishimoto T; Kikutani H
GENE, 133, 2, 163, 169, Nov. 1993, [Peer-reviewed]
English, Scientific journal - Stimulation of RNA polymerase activity by Ginsenoside-Rb2 in diabetic rats
Yokozawa T; Yasui T; Oura H.
PHYTOTHERAPY RESEARCH, 7, 3, 240, 243, May 1993, [Peer-reviewed]
English, Scientific journal - Effect of Ginsenoside-Rb2 on RNA synthesis.
Yokozawa T; Yasui T; Oura H
PHYTOTHERAPY RESEARCH, 7, 1, 68, 71, Jan. 1993, [Peer-reviewed]
English, Scientific journal - Effects of ginsenoside-Rb2 on adenine nucleotide content of rat hepatic tissue.
Yokozawa T; Fujitsuka N; Yasui T; Oura H
JOURNAL OF PHARMACY AND PHARMACOLOGY, 43, 4, 290, 291, Apr. 1991, [Peer-reviewed]
English, Scientific journal
- -
大坪亮太; 安居輝人, Inflammation&Immunity, 30, 2, 34(154), 38(158), Mar. 2022 - An exploration of biomarkers for EBV-induced lymphoproliferative diseases by comprehensive plasma proteomics analysis
大坪亮太; 伊藤寿宏; 今留謙一; 安居輝人, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th, 2021 - 細胞機能を理解する上での構造生物学的アプローチ EBウイルスによるB細胞がん化プログラム
安居 輝人, 生命科学系学会合同年次大会, 2017年度, [2PW07, 5], Dec. 2017
生命科学系学会合同年次大会運営事務局, Japanese - 【慢性炎症性疾患の新たな展開】 慢性炎症と疾患 慢性炎症とウイルス持続感染
安居 輝人, 最新医学, 71, 11月増刊, 2344, 2350, Nov. 2016
(株)最新医学社, Japanese - The RNA-binding protein Mex-3B is required for IL-33 induction in the development of allergic airway inflammation
Y. Yamazumi; O. Sasaki; M. Imamura; T. Oda; Y. Ohno; Y. Shiozaki-Sato; S. Nagai; S. Suyama; Y. Kamoshida; K. Funato; T. Yasui; H. Kikutani; K. Yamamoto; S. Koyasu; T. Akiyama, EUROPEAN JOURNAL OF IMMUNOLOGY, 46, 769, 769, Aug. 2016
English, Summary international conference - 抗体の親和性向上による生体影響の評価に向けた基礎的検討
竹谷 苑子; 長野 一也; 森 宣瑛; 永野 貴士; 向井 美穂; 大須賀 絵理; 芳賀 優弥; 井阪 亮; 鎌田 春彦; 角田 慎一; 南谷 武春; 安居 輝人; 堤 康央, 日本薬学会年会要旨集, 136年会, 3, 144, 144, Mar. 2016
(公社)日本薬学会, Japanese - B細胞内のシグナル伝達機構(第3回) B細胞におけるPKCの生理機能と分子機序
安居 輝人; 南谷 武春, 炎症と免疫, 23, 5, 450, 454, Aug. 2015
(株)先端医学社, Japanese - プロスタグランジンI2アゴニストであるONO-1301はALSモデル動物の神経変性を抑制する
多田 智; 奥野 龍禎; 安居 輝人; 中辻 裕司; 酒井 芳紀; 宮川 繁; 澤 芳樹; 菊谷 仁; 佐古田 三郎; 望月 秀樹, 臨床神経学, 54, Suppl., S99, S99, Dec. 2014
(一社)日本神経学会, Japanese - プロスタグランジンI2アゴニストであるONO-1301はALSモデル動物の神経変性を抑制する
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 酒井 芳紀; 宮川 繁; 澤 芳樹; 菊谷 仁; 佐古田 三郎; 望月 秀樹, 臨床神経学, 53, 12, 1501, 1501, Dec. 2013
(一社)日本神経学会, Japanese - MHV68感染による肺線維症の重篤化とIL-27の役割
有川 智博; 東海林 博樹; 渡部 明子; 義江 修; 伊藤 龍生; 安居 輝人, 金沢医科大学雑誌, 38, 3-4, 156, 156, Dec. 2013
金沢医科大学医学会, Japanese - マウスγヘルペスウイルスはIL‐27依存的に肺炎症を惹起する
渡部明子; 伊藤龍生; 有川智博; 榊原修平; 菊谷仁; 安居輝人; 義江修, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 172, 29 Oct. 2013
Japanese - 【B細胞の分化と機能制御】 胚中心におけるB細胞の反応とBCRシグナル強度
南谷 武春; 菊谷 仁; 安居 輝人, 臨床免疫・アレルギー科, 60, 2, 109, 114, Aug. 2013
(有)科学評論社, Japanese - 新規神経栄養因子としてのB細胞刺激因子(BAFF)
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 望月 秀樹; 佐古田 三郎; 菊谷 仁, 臨床神経学, 52, 12, 1450, 1450, Dec. 2012
(一社)日本神経学会, Japanese - B細胞刺激因子(BAFF)はALSモデル動物の神経変性を抑制する
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 臨床神経学, 51, 12, 1316, 1316, Dec. 2011
(一社)日本神経学会, Japanese - 胚中心の機能と制御 EBウイルスLMP2aによるBCRシグナル変化に伴う胚中心B細胞分化抑制(Impaired germinal center B cell differentiation by altered BCR signal strength with Epstein-Barr virus LMP2a)
南谷 武春; 安居 輝人; 菊谷 仁, 日本免疫学会総会・学術集会記録, 40, 65, 65, Nov. 2011
(NPO)日本免疫学会, English - 炎症/病態 アポトーシス細胞と肥満細胞上のCD300aによる炎症応答の調節(Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor)
小田 ちぐさ; 中橋; 田原 聡子; 安居 輝人; 菊谷 仁; 本多 伸一郎; 渋谷 和子; 長田 重一; 渋谷 彰, 日本免疫学会総会・学術集会記録, 40, 232, 232, Nov. 2011
(NPO)日本免疫学会, English - 免疫が関与する神経疾患 B細胞刺激因子(BAFF)はALSモデル動物の神経変性を抑制する
多田 智; 奥野 龍禎; 安居 輝人; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 日本神経免疫学会学術集会抄録集, 23回, 79, 79, Sep. 2011
日本神経免疫学会, Japanese - 遺伝性ALSのモデル動物におけるリンパ球の役割
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 臨床神経学, 50, 12, 1127, 1127, Dec. 2010
(一社)日本神経学会, Japanese - グリア細胞の神経免疫学 筋萎縮性側索硬化症の病態におけるリンパ球-ミクログリア間相互作用の解析
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 日本神経免疫学会学術集会抄録集, 22回, 53, 53, Mar. 2010
日本神経免疫学会, Japanese - リンパ球の筋萎縮性側索硬化症病態における役割の解析
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 臨床神経学, 49, 12, 1017, 1017, Dec. 2009
(一社)日本神経学会, Japanese - B細胞受容体シグナルと機能発現のリンケージ PKN1はAkt依存性BCRシグナル閾値を制御することによって抗体親和性成熟をコントロールする(PKC-related kinase, PKN1 controls affinity maturation of antibody by regulating BCR signaling threshold dependent on the Akt activation)
安居 輝人; 矢田 佳織; 多田 智; 森本 智美; Mosialos George; Kieff Elliott; 菊谷 仁, 日本免疫学会総会・学術集会記録, 39, 207, 207, Nov. 2009
(NPO)日本免疫学会, English - Fcα/μR欠損マウスにおけるT細胞非依存性抗原に対する液性免疫反応の増強(Enhanced humoral immune responses against T-independent antigens in Fcα/μR-deficient mice)
本多 伸一郎; 栗田 尚樹; 宮本 顕友; 張 愉紀子; 臼井 健太; 竹下 貴恵; 高橋 智; 安居 輝人; 菊谷 仁; 木下 タロウ; 藤田 禎三; 田原 聡子; 渋谷 和子; 渋谷 彰, 日本臨床免疫学会会誌, 32, 5, 445, 445, Oct. 2009
日本臨床免疫学会, English - 筋萎縮性側索硬化症の病態におけるリンパ球の役割の解析
多田 智; 安居 輝人; 奥野 龍禎; 中辻 裕司; 菊谷 仁; 佐古田 三郎, 神経免疫学, 17, 1, 66, 66, Mar. 2009
日本神経免疫学会, Japanese - アレルギー 気道炎症などを中心にして 抗原特異的アレルギー性喘息及び鼻炎に対するSema4Aの抑制的役割(An inhibitory role of Sema4A in antigen specific allergic asthma and rhinitis)
森鼻 哲生; Durubaka Prasad; 安居 輝人; 熊ノ郷 淳; 菊谷 仁, 日本免疫学会総会・学術集会記録, 38, 41, 41, Nov. 2008
(NPO)日本免疫学会, English - ウイルス感染と宿主応答・宿主側の要因 新規アダプター分子STAP-2とEBウイルス産物LMP1の機能的相互作用の解析
池田 収; 関根 勇一; 辻 暁司; 安居 輝人; 杉山 憲司; 吉村 昭彦; 松田 正, 日本免疫学会総会・学術集会記録, 36, 206, 206, Nov. 2006
(NPO)日本免疫学会, Japanese - マウスstrawberry notch homologue遺伝子の解析
坂尾 宣充; 植松 智; 竹内 理; 安居 輝人; 竹田 潔; 改正 恒康; 審良 静男, 日本免疫学会総会・学術集会記録, 35, 60, 60, Nov. 2005
(NPO)日本免疫学会, Japanese - 改変誘導型遺伝子発現システムを用いたEBVのB細胞分化修飾機構の解析
安居 輝人; Kieff Elliott; Luftig Micah; 菊谷 仁, 日本免疫学会総会・学術集会記録, 34, 264, 264, Nov. 2004
(NPO)日本免疫学会, Japanese - エストロゲン欠乏骨粗鬆症におけるT細胞及びCD40を介したT-Bシグナリングの関与
渡辺 研; 内山 也寸志; 杉田 敦子; 武田 聡; 菱谷 彰徳; 安居 輝人; 菊谷 仁; 池田 恭治, 日本骨代謝学会雑誌, 19, 2, 42, 42, Jul. 2001
(一社)日本骨代謝学会, Japanese - リガンド非依存性CD40シグナルはLPS応答に必要である
石田 勲; 安居 輝人; 七條 優子; 坂尾 宣充; 内田 純二; 審良 静男; 菊谷 仁, 日本免疫学会総会・学術集会記録, 30, 72, 72, Nov. 2000
(NPO)日本免疫学会, Japanese - TRAF3欠損マウスにおけるT細胞ネガティブセレクション障害の解析
内田 純二; 安居 輝人; 石田 勲; 吉田 謙二; 熊ノ郷 淳; 菊谷 仁, 日本免疫学会総会・学術集会記録, 30, 91, 91, Nov. 2000
(NPO)日本免疫学会, Japanese - 【免疫2000-01】 シグナル伝達 EBウイルス感染とCD40シグナル
安居 輝人, Molecular Medicine, 37, 臨増 免疫2000-01, 118, 125, Oct. 2000
EBウイルスはB細胞に感染,潜伏し,細胞の形質転換及び腫瘍化を引き起こす.特にEBウイルス遺伝子にコードされる膜タンパク質LMP1は必須の形質転換因子であり,ヒトB細胞においては増殖,分化を誘導する.近年,LMP1の細胞内領域に宿主細胞由来のTRAFが会合することが明らかとなったことより,LMP1がB細胞上に発現する免疫系機能分子CD40の細胞内シグナル伝達経路を利用していることが示唆されてきた.更にLMP1はCD40のシグナルを利用し,巧みにB細胞分化方向を調節することにより,EBウイルスの感染成立に重要な役割を果たしていることが明らかとなってきた, (株)中山書店, Japanese - CD40シグナル改変マウスにおける抗原特異的B細胞の活性化と分化
安居 輝人; 七條 優子; 内田 純二; 菊谷 仁, 日本免疫学会総会・学術集会記録, 29, 263, 263, Oct. 1999
(NPO)日本免疫学会, Japanese - CD40分子の活性化とDetergent-insoluble membranes(DIMs)へのCD40分子の局在化
七條 優子; 安居 輝人; 内田 純二; 菊谷 仁, 日本免疫学会総会・学術集会記録, 29, 262, 262, Oct. 1999
(NPO)日本免疫学会, Japanese - B細胞特異的にCD100/Sema4Dを過剰発現するtransgenic mouseの作成と機能解析
渡辺 知恵; 熊ノ郷 淳; 施 維; 王 暁松; 安居 輝人; 菊谷 仁, 日本免疫学会総会・学術集会記録, 29, 75, 75, Oct. 1999
(NPO)日本免疫学会, Japanese - EB virus(EBV)由来Latent Membrane Protein 1(LMP1)はCD40シグナルをミミックして濾胞外B細胞分化を誘導するが,胚中心形成を阻害する
内田 純二; 安居 輝人; 七條 優子; 菊谷 仁, 日本免疫学会総会・学術集会記録, 29, 117, 117, Oct. 1999
(NPO)日本免疫学会, Japanese - 【臨床遺伝子学'99 免疫研究の最前線】 免疫応答における細胞内情報伝達機構 CD40シグナルと免疫応答
安居 輝人, 最新医学, 54, 増刊, 2267, 2273, Sep. 1999
(株)最新医学社, Japanese - EB virus由来LMP1(Latent Membrane Protein 1)によるB細胞機能発現とCD40シグナルとの比較解析
内田 純二; 村岡 正章; 七條 優子; 安居 輝人; 菊谷 仁, 日本臨床免疫学会会誌, 26回抄録集, 79, 79, Oct. 1998
日本臨床免疫学会, Japanese - CD40シグナル改変マウスにおけるB細胞分化機構の解析
安居 輝人; 村岡 正章; 七條 優子; 内田 純二; 熊ノ郷 淳; 菊谷 仁, 日本臨床免疫学会会誌, 26回抄録集, 98, 98, Oct. 1998
日本臨床免疫学会, Japanese - Subtracted-PCR法を用いたCD40-target geneの同定
施 維; 熊ノ郷 淳; 李 仁淑; 内田 純二; 安居 輝人; 吉田 寛二; 菊谷 仁, 日本臨床免疫学会会誌, 26回抄録集, 375, 375, Oct. 1998
日本臨床免疫学会, Japanese - リンパ球表面分子と免疫調節 CD40とTRAF
安居 輝人; 菊谷 仁, Molecular Medicine, 34, 臨増 免疫1997-98, 98, 104, Sep. 1997
(株)中山書店, Japanese - CD40とCD40L-免疫応答制御におけるシグナル伝達
安居 輝人; 菊谷 仁, 実験医学, 14, 6, 833, 837, Apr. 1996
(株)羊土社, Japanese - ヒトCD40トランスジェニックマウス(hCD40Tg)を用いたCD40シグナルの解析
安居輝人, 日本免疫学会総会 学術集会記録, 1996, 26, 132, 132, 1996 - リンパ球の細胞表面分子とその機能 CD40欠損マウスにおける免疫反応
川部 勤; 鎌仲 正人; 安居 輝人, Molecular Medicine, 32, 臨増, 30, 40, Jun. 1995
(株)中山書店, Japanese - POU転写因子,Epoc-1変異マウスの作製
安居 輝人, 大阪大学医学雑誌, 47, 2, 137, 146, Feb. 1995
大阪大学医学会, Japanese - 糖尿病ラット肝組織中のATP並びにmRNAに及ぼすGinsenoside-Rb2の影響
安居 輝人; 藤塚 直樹; 鳥山 一恵, 和漢医薬学会誌, 7, 3, 444, 445, Mar. 1991
(一社)和漢医薬学会, Japanese - 糖尿病ラットに対するGinsenoside-Rb2のアルブミンmRNA合成に対する影響
安居 輝人, 日本薬学会年会要旨集, 110年会, 3, 71, 71, Aug. 1990
(公社)日本薬学会, Japanese - 糖尿病ラットのATP,albumin mRNAレベルに対するGinsenoside-Rb1の効果
安居 輝人, 生化学, 62, 7, 612, 612, Jul. 1990
(公社)日本生化学会, Japanese - II-A-16 糖尿病ラット肝組織中の ATP 並びに mRNA に及ぼす Ginsenoside-Rb_2 の影響
安居 輝人; 藤塚 直樹; 鳥山 一恵; 横澤 隆子; 大浦 彦吉, 和漢医薬学会大会要旨集, 7, 130, 130, 1990
和漢医薬学会大会, Japanese
■ Lectures, oral presentations, etc.
- Elucidation of SARS-CoV2 entry mechanism by using human functional monoclonal antibodies
Ryota Otsubo; Takeharu Minamitani; Kouji Kobiyama; Shiori Ueno; Ken-Ichi Imadome; Ken Ishii; Kouhei Tsumoto; Wataru Kamitani; Teruhito Yasui
第51回日本免疫学会学術集会, 09 Dec. 2022
07 Dec. 2022 - 09 Dec. 2022 - ヒトモノクローナル抗体を用いたSARS-CoV2エントリー機序の解明
大坪亮太; 南谷武春; 小檜山康司; 今留謙一; 石井健; 津本浩平; 神谷亘; 安居輝人
第69回日本ウイルス学会学術集会, 14 Nov. 2022
13 Nov. 2022 - 15 Nov. 2022 - Comprehensive Plasma Proteome Analysis To Identify for a Biomarker for EBV-Associated Lymphoproliferative Diseases
Ryota Otsubo; Ken-ichi Imadome; Teruhito Yasui
46th International Herpesvirus Workshop, 28 Jul. 2022
25 Jul. 2022 - 29 Jul. 2022 - 包括的血漿プロテオミクス解析によるEBウイルス関連疾患におけるバイオマーカー探索
大坪亮太; 今留謙一; 安居輝人
第35回ヘルペスウイルス研究会, 23 Jul. 2022 - DEVELOPMENT OF RECOMBINANT HB IMMUNOGLOBULIN
R A Furuta; K Yasui; R Tobita; C Toyoda; T Yasui; K Tsumoto; M Satake
ISBT 2022 Virtual Congress
04 Jun. 2022 - 08 Jun. 2022 - ヒト抗破傷風毒素抗体による感染症制御戦略
安居輝人
第95回日本細菌学会総会, 31 Mar. 2022
29 Mar. 2022 - 31 Mar. 2022, [Invited] - ヒト抗破傷風毒素中和抗体開発とその作用機序
大坪亮太; 伊藤寿宏; 安居輝人
第95回日本細菌学会総会
28 Mar. 2022 - 31 Mar. 2022 - Comprehensive proteomics analysis of murine and human plasma for EBV-induced lymphoproliferative diseases
Ryota Otsubo; Toshihiro Ito; Ken-Ichi Imadome; Teruhito Yasui
The 50th Annual Meeting of the Japanese Society for Immunology, 09 Dec. 2021, English, Oral presentation
08 Dec. 2021 - 10 Dec. 2021 - Identification of human herpesvirus microRNA by human blood RNA-Seq
伊藤寿宏; 保井一太; 木村貴文; 田中光信; 大原英剛; 安藤覚; 大坪亮太; 足立淳; 安居輝人
第68回日本ウイルス学会学術集会, Poster presentation
16 Nov. 2021 - 18 Nov. 2021 - An exploration of biomarkers for EBV-induced lymphoproliferative diseases by comprehensive plasma proteomics analysis
大坪亮太; 伊藤寿宏; 今留謙一; 安居輝人
第68回日本ウイルス学会学術集会, Poster presentation
16 Nov. 2021 - 18 Nov. 2021 - Therapeutic strategy for Infectious Diseases through Antibody-based biologics - discovery, optimization and modality
Teruhito Yasui
Infectious Diseases With Novel Modalities, 19 Oct. 2021, English, Public discourse
[Invited] - Comprehensive proteomics analysis for EBV-induced lymphoproliferative diseases
Otsubo Ryota, Ito Toshihiro, Yasui Teruhito
19th International Symposium on Epstein-Barr Virus and associated diseases, Jul. 2021, Poster presentation
29 Jul. 2021 - 30 Jul. 2021 - In silico identification of EBV-encoded microRNAs in human blood
Toshihiro Ito; Kazuta Yasui; Takafumi Kimura; Mitsunobu Tanaka; Hidetaka Ohara; Satoshi Ando; Ryota Otsubo; Teruhito Yasui
19th International Symposium on Epstein-Barr Virus and associated diseases, Jul. 2021, Poster presentation
29 Jul. 2021 - 30 Jul. 2021 - インシリコ解析によるヒト血中ヘルペスウイルスmicroRNAの探索
伊藤寿宏; 保井一太; 木村貴文; 田中光信; 大原英剛; 安藤覚; 大坪亮太; 安居輝人
第34回ヘルペスウイルス研究会, 05 Jun. 2021, Oral presentation
05 Jun. 2021 - 06 Jun. 2021 - EBウイルス誘導性B細胞増殖性疾患モデルマウスを用いた包括的プロテオミクス解析
大坪亮太; 伊藤寿宏; 安居輝人
第34回ヘルペスウイルス研究会, 05 Jun. 2021, Oral presentation
05 Jun. 2021 - 06 Jun. 2021 - Evaluation of humoral immune responses based on comprehensive analysis of B cell responsiveness in human peripheral blood
Takeharu Minamitani; Tetsuro Kosizuka; Naoki Inoue; Teruhito Yasui
第13回次世代アジュバント研究会, 21 Jan. 2020, Poster presentation - サイトメガロウイルスに対するヒト液性免疫応答の網羅的解析
南谷武春; 腰塚哲朗; 井上直樹; 安居輝人
第67ウイルス学会学術集会, 30 Oct. 2019, Poster presentation - Comprehensive analysis for the immunogenicity of HCMV proteins in human
Takeharu Minamitani; Rika Furuta; Ken-ichi Imadome; Teruhito Yasui
44th Annual International Herpesvirus Workshop, Jul. 2019, Poster presentation
20 Jul. 2019 - 24 Jul. 2019 - EBVの免疫病態発現機構解明とバイオロジクス開発への応用
安居輝人
くすりのシリコンバレーTOYAMA創造コンソーシアム医薬品研究セミナー, 11 Jul. 2019, Public discourse
[Invited] - CMVに対するヒト液性免疫応答の網羅的解析
南谷武春; 腰塚哲朗; 井上直樹; 安居輝人
第33回ヘルペスウィルス研究会, 20 Jun. 2019, Japanese, Oral presentation
[Domestic Conference] - コンソーシアム事業研究開発プロジェクトの紹介＜ 創薬（免疫学）分野＞
安居 輝人
「くすりのシリコンバレーTOYAMA」創造コンソーシアムキックオフシンポジウム, 19 Mar. 2019, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - ヒトリキッドバイオプシーから臨む診断薬/治療抗体シーズの情報集積技術
安居 輝人
薬事講演会, 05 Mar. 2019, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - Biology camphor tree development strategy based on man immunity primitivity
Yasui Teruhito
Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, Japanese, Oral presentation
[Domestic Conference] - サイトメガロウイルスの網羅的ヒト免疫原性解析
南谷武春; 古田里佳; 今留謙一; 安居輝人
第66回日本ウイルス学会学術, 28 Oct. 2018, Japanese, Poster presentation
[Domestic Conference] - EBウイルスLMPシグナルによる節外性リンパ腫形成
Teruhito Yasui
15th EB Virus Workshop, 14 Jul. 2018, Japanese, Oral presentation
Yamaguchi, Japan, [Domestic Conference] - Concurrent expression of EBV LMP1 and LMP2A in germinal center B cells induces lymphomagenesis in mouse model
MINAMITANI Takeharu
International Conference on EBV & KSHV 2018, Jul. 2018, English, Poster presentation
Maqdison, WI, USA, [International presentation] - CMVに対する網羅的ヒト免疫原性解析
Takeharu Minamitani; Rika Furita; Kenichi Imadome; Teruhito Yasui
Herpes Virus Workshop, Jun. 2018, Japanese, Oral presentation
Fukuoka, Japan, [Domestic Conference] - ヒト免疫原性に基づいた感染症関連バイオロジクス探索技術
Teruhito Yasui
Medical Japan Osaka 2018, Feb. 2018, Japanese, Public discourse
Osaka, Japan, [Invited], [Domestic Conference] - ヒト免疫機構を基盤とした免疫駆動型バイオロジクス ―ワクチンターゲット探索と感染症関連抗体医薬品開発―
Teruhito Yasui
平成29年度第3回「ワクチン用新規アジュバント開発のための基盤研究プロジェクト」進捗状況報告会, Feb. 2018, Japanese, Oral presentation
Toyama, Japan, [Invited], [Domestic Conference] - EBウイルスによるリンパ増殖性疾患発症機構の解明
Teruhito Yasui
13th Medical Department Science Forum of Primates, Nov. 2017, Japanese, Public discourse
Ibaraki, Japan, [Invited], [Domestic Conference] - EBV LMP1 and LMP2A coordinately induce EBV-associated lymphoproliferative diseases in mouse model
Takeharu Minamitani; Yijie Ma; Hiroshi Kida; Chao-Yuan Tsai; Masanori Obana; Daisuke Okuzaki; Yasushi Fujio; Atsushi Kumanogoh; Hitoshi Kikutani; Elliott Kieff; Benjamin E. Gewurz; Teruhito Yasui
The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, English, Oral presentation
Osaka, Japan, [Domestic Conference] - The concerted impact of Epstein-Barr Virus LMP1 and LMP2A on the virus-induced lymphoproliferative diseases in mouse model
Takeharu Minamitani; Yjie Ma; Hufeng Zhou; Hiroshi Kida; Chao-Yuan Tsai; Masanori Obana; Daisuke Okuzaki; Yasushi Fujio; Atsushi Kumanogoh; Bo Zhao; Hiroshi Kikutani; Elliott Kieff; Benjamin E Gewurz; Teruhito Yasui
42nd Annual International Herpesvirus Workshop, Aug. 2017, English, Oral presentation
Ghent, Belgium, [Domestic Conference] - EBウイルスLMP1とLMP2Aの協調的発現はT/NK細胞と競合的にリンパ腫プロセスを誘導する
南谷武春; Yijie Ma; Hufeng Zhou; 木田博; Chao-Yan Tsai; 尾花理徳; 奥崎大介; 藤尾慈; 熊ノ郷淳; Bo Zhao; 菊谷仁; Elliott Keff; Benjamin E. Gewurz; 安居輝人
14th EB Virus Workshop, Jul. 2017, Japanese, Oral presentation
Hokkado, Japan, [Domestic Conference] - 胚中心B細胞におけるEBウイルスLMP1とLMP2Aの協調的発現がリンパ増殖性疾患を誘導する
Takeharu Minamitani; Teruhito Yasui
31th Herpes Virus Workshop, Jun. 2017, Japanese, Oral presentation
Shimane, Japan, [Domestic Conference] - Epstein-Barr virus LMP2A modifies the affinity-based selection of B cells in germinal centers
T. Minamitani; T. Yasui; Y. Ma; H. Zhou; D. Okuzaki; C.-Y. Tsai; S. Sakakibara; B.E.Gewurz; E. Kieff; H. Kikutani
17th International Symposium o Epstein Barr virus and associated diseases., Aug. 2016, English, Oral presentation
Zurich, Switzerland, [International presentation] - LIP/DDP法を用いたEBVのヒト免疫原性探索
Takeharu Minamitani; Rika Furita; Kawa Takayo; uhito Yasui
30th Herpes Virus Workshop, Jun. 2016, Japanese, Oral presentation
Tokyo, Japan, [Domestic Conference] - Antigen-specific maturation of anti-nuclear antibodies in systemic lupus erythematosus
Shuhei Sakakibara; Kazuya Takeda; Teruhito Yasui; Masashi Narazaki; Toshio Tanaka; Hitoshi Kikutani
Nov. 2015 - Akt/mTOR axis in antigen-committed B cells regulates IgA+ plasma cell differentiation
Takeharu Minamitani; Shuhei Sakakibara; Tsai Chao-Yuan; Hitoshi Kikutani; Teruhito Yasui
Nov. 2015 - Inhibition of germinal center formation and humoral immune responses by EB virus protein LMP1.
Tsai, C.-Y; T.Yasui; T. Minamitani; K. Morita; S. Sakakibara; H. Kikutani
15th International Congress of Immunology, Aug. 2013, English, Poster presentation
[International presentation] - Epstein-Barr virus-encoded latent membrane protein 2A impairs B cell selection in germinal centers but not germinal center formation.
Minamitani, T; S. Sakakibara; T. Yasui; H. Kikutani
15th International Congress of Immunology, Aug. 2013, English, Oral presentation
[International presentation] - Generation of autoreactive and polyreactive antibody producing cells during gamma-herpesvirus infection
Shuhei Sakakibara; T. Yasui; T. Minamitani; H. Jinzai; H. Kikutani
15th International Congress of Immunology, Aug. 2013, English, Poster presentation
[International presentation]
■ Research Themes
- クライオ電顕を用いた時分割構造解析による破傷風毒素の膜侵入機構解明
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
井上 豪; 安居 輝人
本申請では、還元型（不活性型）の破傷風毒素（TeNT）をクライオ電顕で用いるグリッドに固定化し、低pH下で酸化剤を添加して酸化型（活性型）へと構造変化させた場合の変化の過程を低温トラップ法で解析し、中枢神経系のみで膜侵入が起こる分子機構について考察することを目的としている。
本目的を達成するためには、令和３年度に導入したクライオ電顕を稼働させる必要があったが、原因不明のトラブルが続き、その解決に3年を費やしている。最終的にカメラとそれを制御するボードの総入れ替えによって漸く稼働しはじめ、24時間のテスト撮影が続いている。この間、本研究課題の標的であるTeNTの大量精製も進み、酸化体のTeNTの粒子像を撮影するための凍結条件の検討も進んでいる。
一方、他の測定装置を用い、クライオ電顕グラフェンの酸化修飾によってエポキシ基を導入した初代のクライオ電顕用の新規グリッド（Epoxidized Graphene Grid; EG-grid, Scientific Reports, 2023）を改良して、Hisタグを認識したり、マルトース結合蛋白質を認識したりする次世代型のEG-gridの開発にも成功している（未発表）。グラフェン膜上にタンパク質を効率よく固定化する技術の開発も進んでおり、EG-Grid上で破傷風毒素(TeNT)を固定化することについても計画通り実験を実施できる目途が立っている。還元剤の入った反応溶液と混合することで、構造変化を起こさせ、その直後に凍結することで、低温トラップによる構造変化をクライオ電子顕微鏡で捉える実験を進める予定である。
日本学術振興会, 基盤研究(B), 大阪大学, 23K23821 - 多様な臍帯血と脳性まひへの他家造血幹細胞治療の可能性
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
田中 えみ; 安居 輝人
日本学術振興会, 基盤研究(C), 大阪公立大学, 22K07850 - クライオ電顕を用いた時分割構造解析による破傷風毒素の膜侵入機構解明
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
井上 豪; 安居 輝人
日本学術振興会, 基盤研究(B), 大阪大学, 22H02557 - Study on pathogenesis of invasive pneumococcal disease by different serotypes
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2024
大石 和徳; 金谷 潤一; 磯部 順子; 安居 輝人
1．In vitro 経細胞間移動(bacterial transcytosis; BT)アッセイ
ヒト血管内皮細胞(HUEhT-2)、ヒト鼻腔上皮細胞（HNEpC）、脳微小血管内皮細胞(TY09細胞)を使用し、各上皮細胞をトランスウェルチャンバーのインサート（3μmポア）上で一晩培養し、上層に血清型の異なる肺炎球菌を接種し、300xg, 5分遠心後に、1時間静置し（上層にはgentamicin 20 μg/ml添加）、上層から下層に移動した菌数をカウントし、BT(％)を算定した。アッセイに使用する肺炎球菌株として、侵襲性肺炎球菌感染症の原因菌の中から、高侵襲性と想定された12F, 10A, 23A,低侵襲性と想定された3, 19Aの5つ血清型を選択した。複数回のアッセイ実施の結果、HUEhT-2> HNEpC> TY09の順にBT%が高かった。この結果から、細胞の種類、血清型によって、BT(%)が異なる可能性が示唆された。また、TY09ではBT(%)が最も低かった所見はBlood-brain CSF barrierの透過率が低いことを示唆している可能性が考えられた。また、血清型 3 のBT%は、他の血清型12F, 10A, 23A, 19Aと比較して低かった。
2．RNA seq（トランスクリプトーム）解析
ヒト血管内皮細胞(HUEhT-2)を肺炎球菌生菌で1時間共培養し、細胞を洗浄後にRNA seq解析を行った。RNA発現量変化のクラスタリング解析により、血清型3と23A間での細胞応答に差は認められなかった。さらに、パスウェイ解析では菌処理した細胞において、未処理細胞と比較して、アポトーシスを含め細胞死関連パスウェイや血管形成や血管新生関連パスウェイ、細胞構成タンパクに関わるパスウェイの変化が認められた。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Toyama Institute of Health, 21K08503 - The prediction of the clinical records for infectious diseases by tracking the diversity of Immuoglobulin gene mutation
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
YASUI TERUHITO
Human acquired immune responses includes B cell differentiation in which immunoglobulin (Ig) genes undergo somatic mutations against pathogen infection. However, it has not been understood how fast and ordered Ig gene got mutations in response to the infections. To elucidate molecular mechanisms in which the human immune responses regulates Ig affinity, pathogen-induced Ig gene mutation was analyzed with molecular biological approach. As a result, we were able to identify the numbers and hot spots in the Ig gene mutations induced by vaccine components, and viral proteins derived from persistent infections. Collectively, the findings in this project indicate persistently viral infection always maintains the humoral immune responses through the continuous stimulation by viral proteins that the reactivation provides in human.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, National Institutes of Biomedical Innovation, Health and Nutrition, 16K14650 - Elucidation of the correlation between the structure of the membrane protein LMP1 derived from EB virus and its function of latent infection
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2017
Inoue Tsuyoshi
Mice expressing membrane proteins LMP1 and LMP2A derived from EV virus were prepared and their effects were investigated. It was found that LMP2A promotes the differentiation of germinal center B cells into antibody producing cells and contributes to infection of EBV by surviving low affinity B cells. In addition, systemic lupus erythematosus-like symptoms were induced and firstly proved to be associated with autoimmune diseases.In addition, T / NK cells were reduced by using its antibody, and the pathological condition of the mouse was analyzed in the state of immunosuppression. It was found that LMP1 and LMP2A cooperate with each other in germinal center B cells and induce proliferative diseases such as Hodgkin's lymphoma.
The crystallization of the C-terminus region of CTAR1 involved in signal transduction in LMP1 was performed. The complex crystals between CTAR1 and its antibody of 11A1 up to 1.9 A resolution were obtained and the structural analysis is now in progress.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 25282230 - Study on the chronic inflammation and cell growth transformation induced by gammaherpesvirus infection
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
YASUI Teruhito
Epstein-Barr virus (EBV) infects into the 90 % of human being in the world-wide and is thought to a causative agent for some malignancies. Of the EBV-coding genes, Latent membrane protein (LMP) has been known to be involved in the tumorigenesis. Here this study demonstrates that molecular pathogenesis by which both LMP1 and LMP2a expression in B cells gives rise to lymphomagenesis. Depletion of T cells resulted in the development of splenomegaly induced by aberrant B cell growth. In conclusion, this study clearly indicates that T cells is responsible for the regulation of EBV-induced cell growth transformation in vivo.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 24590550 - Roles of guidance factors in immune regulation
Grants-in-Aid for Scientific Research
2008 - 2012
KIKUTANI Hitoshi; YASUI Teruhito; MIZUI Masayuki; SAKAKIBARA Shuhei
This study has been carried out to determine roles of semaphorins and their receptors in immune regulation. We showed that Sema4A and Sema3A play roles in negative regulation in allergic immune responses and in trafficking of dendritic cells from the periphery to lymph nodes, respectively. Tim-4 was also shown to play a regulatory role in T-cell mediated immunity. Furthermore, PKN1, a serine-threonine kinase, whose functions had been unknown, turned out to be necessary not only for regulation of B cell antigen receptor signals and but also for selection of high affinity antibody producing B cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (S), Osaka University, 20229007 - Elucidation of the molecular mechanism how EB virus induces the pathogenesis by visualizing viral infection
Grants-in-Aid for Scientific Research
2009 - 2011
YASUI Teruhito; KIKUTANI Hitoshi
Epstein-Barr virus is an oncogenic herpesvirus that infects into over 90% of worldwide human beings. To elucidate the molecular pathogenesis in which EB virus induce cell growth transformation, recombinant EB virus was produced to visualize the viral infection and then utilized for identification of host factor that is responsible for the viral entry. Furthermore, the novel cloning strategy for identifying host molecules associated with latent membrane proteins was established to clarify the contribution of the interacting host factor in EB virus infection.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 21590509 - The comprehensive analysis of molecular mechanism by which EB virus LMP1 gene induces cell growth transformation
Grants-in-Aid for Scientific Research
2007 - 2008
YASUI Teruhito
本研究ではEBV発がんの分子機構を包括的に解明するために、EBV潜伏感染遺伝子Latent membrane protein (LMP1、LMP2aのB細胞形質転換機構の分子作用メカニズムの解析を行った。1)LMP-LMP2a間タンパク相互作用の解析とハイスループット(HTS) 抗LMP作用薬剤スクリーニング法確立の試み、2)LMP1シグナルに関与する宿主因子の同定に焦点を絞り解析した。その結果、LMP両分子間の直接的相互作用を証明するために、Bimolecular Fluorescence Complementation (BiFC)法を行い、蛍光強度の発現を検討することによって、LMP1-LMP2a分子相互作用の有無を検討した。その結果、LMP1間、LMP2a間及びLMP1-LMP2a間相互作用が存在することが明らかとなった。一方、LMP下流シグナルに関与する可能性のある7分子を同定した。いずれの分子もLMPの発現により細胞内局在を変化させることが明らかとなった。特にLMP依存性B細胞形質転換作用に関与する細胞増殖・生存制御を司る推定分子としてp73結合分子Ranbp9がLMP下流シグナルに存在することが示唆された。1)項のハイスループット(HTS) 抗LMP1作用薬剤スクリーニング法確立の試みに関連して、B細胞生存に関与するTRAF3とLMP1との相互作用に焦点を当て、最終的にEBV阻害薬の候補薬剤を選別するシステムの基盤構築を試みた。LMP1は細胞膜表面上でTRAF3と恒常的に会合することが明らかとなっているが、申請者らはTRAF3の細胞内局在はN-末端側RINGフィンガードメインに規定されていることを明らかにした。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 19590474 - Overcome of virus-induced neurological disorders : a novel strategy based on the functions of a pattern recognition receptor, RAGE
Grants-in-Aid for Scientific Research
2006 - 2007
TOMONAGA Keizo; IKUTA Kazuyoshi; TANIYAMA Hiroyuki; YASUI Teruhito
Borna disease virus (BDV) belongs to the Bornaviridae family, within the nonsegmented negative-strand RNA virus, Mononegavirales, which is characterized by highly neurotropic, noncytopathic replication, and persistent infection. Although previous studies using rodent models indicated that modulation of the immune response could contribute to the induction of persistence in the brain, the mechanisms by which CNS viruses efficiently control immune response have not been yet fully elucidated. Furthermore, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this study, we investigated the role of a pattern recognition receptor, RAGE (receptor for advanced glycation end products), which is involved in the immune system's response pathways, as well as an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. A prominent role of S100B appears to be the promotion of vascular inflammatory responses through interaction with the RAGE. We demonstrated that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even on incitation with several inflammatory stimuli, including lipopolysaccharide. In addition, the expression of the vascular cell adhesion molecule, VCAM-1, as well as the infiltration of encephalitogenic T-cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S1008 in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 18390139 - Study on the mechanism by which EB virus LMP genes modify B cell development in host
Grants-in-Aid for Scientific Research
2005 - 2006
YASUI Teruhito
Epstein-Barr virus (EBV) has tropism for the human B lymphocytes and epithelial cells and widely infects into 95% of human being in the world-wide. It is also known that EBV is a causative reagent to be associated with Burkitt's lymphomas, Hodgkin's lymphomas, AIDS-associated lymphomas. EBV escapes immunosurveillance when it infects and induces its tumorigenicity in B lymphocytes but little is known about the molecular mechanisms by which EBV invades well in human. lb clarify the mechanism, here we tried to show how EBV latent gene products contribute to EBV-induce B cell growth transformation and activation in viva First of all, we generated transgenic mice (tg) with B cell-specific expression of EBV nuclear antigen (EBNA1) which is involved in the EBV genome maintenance in cells and the growth transformation by stabilizing p53 tumor suppressor protein. They carry EBV EBNA1 gene under the control of Ig enhancer/polyoma immediate early gene promoter to give EBNA1 expressed in B cells specifically. EBNA1tg showed hyperplasia in the spleen and lymph nodes where B cells express large amount of EBNA1 protein. There is no difference in the incidence of tumorigenicity between EBNA1tg and the control suggesting that tumorigenicity of EBV would be dependent on the other EBV latent gene such as LMP1 and EBNA1 and that it could be on the diversity of genetic background in human which is susceptibility for EBV. The second aspect was that how in vivo system could be established for searching the pathogenesis of EBV on B cell growth transformation induced by latent membrane proteins (LMP). The data have been shown that the expression of LMP including LMP1 and LMP2a inhibit and modify B cell development at the late stage, especially, the transition of follicular B cells to germinal center B cells in secondary lymphoid organs. In this context, it is difficult to determine the involvement of LMP in lymphomagenesis to develop Burkitt's lymphomas, Hodgkin's lymphomas which are thought to be derived from germinal center B cells. lb overcome the difficulties, we developed more sophisticated drug-inducible LMP expression system in mouse where early B cell development was defective in inducing LMP1 expression suggesting that LMP1 is responsible for escaping host immunosurveillance in the EBV infection.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 17590417 - 免疫系ホメオスターシスを制御するシグナルの解析
科学研究費助成事業
2001 - 2005
菊谷 仁; 安居 輝人
セマフォリンファミリーは、神経回路形成過程において機能するガイダンス因子として同定された分子群であるが、申請者らの研究から、種々のセマフォリン分子が免疫反応の成立や調節において重要な役割を果たしていることが明らかになってきた。本研究は、これら分子のin vitro、in vivoにおける免疫学的活性、それらの受容体の同定やシグナル伝達経路の解析を行い、本年度は以下の研究成果を得た。
(1)昨年度までに、Sema4A欠損マウスを作成とその解析から、樹状細胞上のSema4AがT細胞のプライミングにおいてT細胞上のSema4AがTh1分化において必要であることを示した。本年度は、遺伝的背景がBALB/cのSema4A欠損マウスを解析し、Sema4A非存在下ではTh2反応が亢進し、アレルギー様の皮膚炎が自然発症することが明らかになった。また、ヒトの多発性硬化症により近い自己免疫性脳脊髄炎(EAE)を発症するSJLマウスを用いて、抗Sema4A抗体による発症阻止実験を行った。その結果、抗Sema4A抗体がSJLマウスにおける再発性の脳脊髄炎の発症を阻止できることを示した。
(2)昨年度作成したPlexin-A1欠損マウスを更に詳細に解析した。その結果、Plexin-A1欠損マウスにおいては樹状細胞の機能や抗原特異的なT細胞分化が著しく低下しているのに加え、破骨細胞の分化不全から大理石病を発症することが明らかになった。また、Plexin-A1欠損樹状細胞はSema6Dに対する結合性や、Sema6Dによるサイトカイン産生が著明に減弱しており、樹状細胞の活性化においてSema6D-Plexin-A1相互作用が重要な働きを果たしていると考えられる。
日本学術振興会, 特定領域研究, 大阪大学, 13140204 - Regulation of immune responses and CD40 signal
Grants-in-Aid for Scientific Research
1999 - 2000
KIKUTANI Hitoshi; KUMANOGOH Atsushi; YOSHIDA Kenji
1) CD40 was found to play a role in LPS responses in a ligand-independent manner because macrophages and B cells from CD40-deficient mice but not from CD40 ligand-deficient mice displayed impaired responses to LPS.Biochemical studies revealed that CD40 was associated with TLR4 upon stimulation with LPS, suggesting that CD40 is involved in LPS signaling as one of LPS receptor components.
2) CD100 was found to induce dephosphorylation of its lymphocyte receptor, CD72, and dissociation of a tyrosine phosphatase, SHP1 from CD72. This finding indicates that CD100 turns off negative signaling of CD72, resulting in augmentation of B cell activation.
3) CD100-deficient mice showed not only poor B cell responses but also impaired T cell priming. Furthermore, it was found that impaired T cell priming was due to a defect of activation of antigen presenting cells such as dendritic cells in the absence of CD100.
4) We demonstrated that CD100 was proteolytically cleaved and released from T and B cells as functional soluble CD100 upon activation of cells. Serum levels of soluble CD100 increased after immunization of normal mice or after the onset of autoimmune diseases of MRL/lpr mice. Furthermore, serum levels of soluble CD100 were found to well correlate with titers of specific antibodies or titers of auto-antibodies in these mice.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B)., Osaka University, 11470087 - リンパ球の正常及び異常増殖と副刺激シグナル
科学研究費助成事業
1999 - 1999
菊谷 仁; 熊ノ郷 淳; 吉田 謙二; 安居 輝人
1.細胞質内領域に種々の欠失やアミノ酸置換を持つ変異CD40のみを発現する変異マウスを作製し、それらの免疫能の解析から、CD40からは膜近位部と膜遠位部の少なくとも二種のシグナルが伝達され、B細胞の活性化、分化とクラススイッチには膜近位部からのシグナル、胚中心形成には膜遠位部からのシグナルが必要であることを示した。
2.CD40欠損マウスには、腫瘍ワクチンで抗腫瘍CD4T細胞を誘導できないが、腫瘍ワクチンと同時にCD40刺激した樹状細胞を接種すると、CD40欠損マウスにおいても抗腫瘍免疫が誘導された。すなわち、腫瘍ワクチンによる抗腫瘍T細胞の誘導にはCD40シグナルによって樹状細胞が活生化されることが必須である事を示した。
3.EBウイルスの形質転換因子LMP1をB細胞特異的に発現するトランスジェニックマウスのB細胞機能や免疫能を解析し、LMP1がCD40シグナルと同様にクラススイッチを含むリンパ濾胞外でのB細胞活性化と分化を誘導するが、一方でCD40とは異なり胚中心B細胞分化を抑制することを示した。
4.CD40シグナルの標的遺伝子の一つとしてCD100遺伝子を単離し、CD100刺激はCD40で誘導される増殖や免疫グロブリンのクラススイッチを増強すると共に、in vivoでも抗体産生を増強する事を示した。さらに、CD100の受容体としてplexin-B1に加え、リンパ球上ではCD72が低親和性受容体として機能している事を明らかにした。
5.CD100欠損マウスやCD100トランスジェニックマウスを作製し、CD100が、CD5陽性のB1細胞が分化、CD40やLPSに対するB細胞の反応性、T細胞依存性抗原に対する抗体産生反応に必要である事を示した。
日本学術振興会, 特定領域研究(A), 大阪大学, 09256208 - Mechanisms of regulation of immune responses by CD40-CD40L interactions.
Grants-in-Aid for Scientific Research
1997 - 1998
KIKUTANI Hitoshi; KUMANOGOH Atsushi; YOSHIDA Kenji; YASUI Teruhito
A critical role of CD40-CD154 (CD40 ligand) interactions in humoral immune responses has been previously demonstrated by the deficiency of CD40, or CD154 in the mouse or human. To further dissect CD40 signals in antigen-driven B cell differentiation, we have attempted to reconstitute CD40-CD154 interactions in CD40-deficient mice by expressing various mutant CD40 transgenes under the control of Ig promtor/enhancer. The expression of the deletion mutant carrying only the membrane proximal region could rescue B cell differentiation in the extra-follicular area (PALS) including Ig class switching but not germinal center (GC) formation. GC formation was dependent on signals from the membrane distal region including TRAF2, 3 and 5 binding site of CD40.
The latent membrane protein 1 (LMP1), which is a transforming gene product of Epstein Barr virus (EBV), is known to bind TRAF proteins. The transgenic mice expressing LMP1 in a B cell-specific manner were crossed with CD40-deficient mice. The transgenic expression of LMPl could rescue Ig class switch but not germinal center formation of CD40-deficient mice. The affinity of antibodies produced in these mice was considerably low. It thus appears that LMP1 partly share signals with CD40.
The development of autoimmunity is often observed in patients with X-linked hyper IgM syndrome caused by defects in the CD154 gene, however, this phenomenon can not be simply explained by known functions of CD40 or CD154. To explore the mechanism how autoirnmunity develops in the absence of CD4O-CD154 interactions, we transferred T cells of CD40 (-/-) BALB/c mice into BALBc nu/nu mice, so that CD40-CD 154 interactions can be reconstituted in recipient mice. The recipients that received T cells from CD40 (-/-) but not from normal BALB/c produced various autoantibodies and developed autoimmune gastritis and sialoadenitis. Autoimmunity could be transferred by CD4^+ T cells but not CD8^+ T cells. CD40 (-/-) mice have reduced numbers of CD45RB^CD4^+T cells that are known to consist of memory/effector T cells and regulatory T cells. Co-transfers of CD4^+ T cells from normal BALB/c could prevent development of autoiminunity induced by T cells of CD40 (-/-) mice. It thus appears that CD40-CD 154 interactions are also required for generation of regulatory T cells that suppress autoreactive T cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 09470095 - The CD40-CD40 ligand interaction in humoral and cellular immune responses.
Grants-in-Aid for Scientific Research
1996 - 1996
KIKUTANI Hitoshi; YASUI Teruhito
The CD40-CD40 ligand (CD40L) interaction is known to be essential for humoral immune responses. It has also been recently suggested that CD40 on antigen presenting cells play an important role in T cell activation. To elucidate a role of CD40 in T cell activation/differentiation, we studied immune responses of CD40-deficient mice against Leishmania major, a resolution of which is known to be dependent on a Th1 T cell response. Our results demonstrated that CD40-deficient mice were susceptible to L.major infection.
Furthermore, it turned out that the mutant mice mounted a Th2 response to the parasites instead of a Th1 response because of an absence of CD40-dependent IL-12 production by antigen-presenting cells. The role of CD40 in generation of effector T cells could be demonstrated in vitro. T cells from OVA-specific TCR transgenic mice were stimulated with OVA peptides in the presence of CD40-positive or negative APC.Certain concentrations of peptides could induce generation of IFN-g producing Th1 cells in the presence of CD40-positive APC but not in the presence of CD40-negative APC while IL-4 producing Th2 cells could be induced by both CD40-positive and CD40-negative APC with appropriate concentrations of peptides. Moreover, addition of IL12 could rescue the generation of Th1 cells in the presence of CD40-negative APC.These results suggest that CD40-dependent IL-12 production by APC may be critical in generation of Th1 effector cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 08457107
