Biological significance and molecular basis of lectin receptor-mediated self-recognition

• Project/Area Number: 20H00505
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Yamasaki Sho 大阪大学, 微生物病研究所, 教授 (40312946)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000); Fiscal Year 2022: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000); Fiscal Year 2021: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000); Fiscal Year 2020: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
• Keywords: レクチン受容体 / Mincle / ミクログリア / C型レクチン受容体 / β-GlcCer / ゴーシェ病 / 内因性リガンド

Outline of Research at the Start

本研究はＣ型レクチン受容体（CLR）が担う自己認識に焦点を絞り、新たに見出された相互作用を中心に、その生物学的意義と分子基盤を明らかにすることを目的とする。生体は、常に自己・非自己双方に起因する様々な「危機」に曝されている。CLRはパターン認識受容体ファミリーに分類されるが、病原体のみならず自己由来のリガンドを認識して免疫応答を発動する特徴的な機能を持つことを見出されてきた。生体の異変に対処する有益な恒常性維持機構であると推測されるが、自己認識に伴う生体応答の生理的・病理的役割は明確でなく、未だ内因性リガンドが同定されていないCLR ファミリー分子も多い。そこで本研究ではその詳細を明らかする。

Outline of Final Research Achievements

Gaucher disease (GD) is the most common lysosomal storage disease caused by recessive mutations in the degrading enzyme of β-GlcCer. However, it remains unclear how β-GlcCer causes severe neuronopathic symptoms, which are not fully treated by current therapies. We herein found that β-GlcCer accumulating in GD activated microglia through Mincle to induce phagocytosis of living neurons, which exacerbated Gaucher symptoms. This process was augmented by TNF secreted from activated microglia that sensitized neurons for phagocytosis. This characteristic pathology was also observed in human neuronopathic GD. Blockade of these pathways in mice with a combination of FDA-approved drugs, minocycline and etanercept, effectively protected neurons and ameliorated neuronopathic symptoms. In this study, we propose that limiting unrestrained microglia activation using drug repurposing provides a quickly applicable therapeutic option for fatal neuronopathic GD.

Academic Significance and Societal Importance of the Research Achievements

ゴーシェ病はグルコシルセラミドと呼ばれる糖脂質が蓄積することで発症する遺伝性難病である。致死性の神経症状を合併するが、詳細な分子メカニズムは不明で有効な治療法が存在しない。本研究では、グルコシルセラミドによって脳の免疫細胞であるミクログリアが直接活性化され、神経細胞を食べてしまうことで神経細胞が減少し、致死性の障害に繋がることを明らかにした。本研究成果により、ゴーシェ病の新たな治療法が見出され、これまで治療法がなかった致死性の神経型ゴーシェ病を先天的に患う小児患者やその家族に希望を与えるものと期待される。

Research Products

• [Journal Article] Immunomodulatory Functions of Glycolipids from Pathogens (2023)
  • Author(s): Guenther Carla、Watanabe Miyuki、Yamasaki Sho
  • Journal Title: Methods Mol. Biol., Glycolipids Methods and Protocols Volume: 2613 Pages: 23-31
  • DOI: 10.1007/978-1-0716-2910-9_3
  • ISBN: 9781071629093, 9781071629109
• [Journal Article] The kinetics of signaling through the common FcRγ chain determine cytokine profiles in dendritic cells (2023)
  • Author(s): Watanabe Miyuki、Motooka Daisuke、Yamasaki Sho
  • Journal Title: Science Signaling Volume: 16 Issue: 775
  • DOI: 10.1126/scisignal.abn9909
  • Peer Reviewed
• [Journal Article] Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary <i>Aspergillus fumigatus</i> Infection by Regulating Natural Killer Cell Survival (2023)
  • Author(s): Yoshikawa F?bio S.Y.、Wakatsuki Maki、Yoshida Kosuke、Yabe Rikio、Torigoe Shota、Yamasaki Sho、Barber Glen N.、Saijo Shinobu
  • Journal Title: Journal of Innate Immunity Volume: 1 Issue: 1 Pages: 1-15
  • DOI: 10.1159/000527188
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Direct activation of microglia by β-glucosylceramide causes phagoptosis of neurons that exacerbates Gaucher disease. (2023)
  • Author(s): Shimizu T, Schutt C R, Izumi Y, Tomiyasu N, Omahdi Z, Kano K, Takamatsu H, Aoki J, Bamba T, Kumanogoh A, Takao M, Yamasaki S*.
  • Journal Title: Immunity Volume: 56 Issue: 2 Pages: 1-13
  • DOI: 10.1016/j.immuni.2023.01.008
  • Peer Reviewed / Open Access
• [Journal Article] 6-C-Linked trehalose glycolipids signal through Mincle and exhibit potent adjuvant activity (2023)
  • Author(s): Thathsaranie P. Manthrirathna M.A.、Kodar Kristel、Ishizuka Shigenari、Dangerfield Emma M.、Xiuyuan Lu、Yamasaki Sho、Stocker Bridget L.、S. M. Timmer Mattie
  • Journal Title: Bioorganic Chemistry Volume: 133 Pages: 106345-106345
  • DOI: 10.1016/j.bioorg.2023.106345
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ligand‐Controlled Stereoselective Synthesis and Biological Activity of 2‐Exomethylene Pseudo‐glycoconjugates: Discovery of Mincle‐Selective Ligands (2023)
  • Author(s): Ikazaki Takahiro、Ishikawa Eri、Tamashima Hiroto、Akiyama Hisako、Kimuro Yusuke、Yoritate Makoto、Matoba Hiroaki、Imamura Akihiro、Ishida Hideharu、Yamasaki Sho、Hirai Go
  • Journal Title: Angewandte Chemie International Edition Volume: e202302569 Issue: 22
  • DOI: 10.1002/anie.202302569
  • Peer Reviewed
• [Journal Article] SARS-CoV-2に対するT細胞免疫 (2023)
  • Author(s): 坂井由葵, 山﨑晶
  • Journal Title: 実験医学 Volume: 41 Pages: 521-526
• [Journal Article] Fungal β‐mannosyloxymannitol glycolipids and their analogues: synthesis and Mincle‐mediated signaling activity (2022)
  • Author(s): Matsumaru T.、Sakuratani K.、Yanaka S.、Kato K.、Yamasaki S.、Fujimoto Y.
  • Journal Title: European Journal of Organic Chemistry Volume: - Issue: 20
  • DOI: 10.1002/ejoc.202200109
  • Peer Reviewed
• [Journal Article] Synthetic vaccines targeting Mincle through conjugation of trehalose dibehenate (2022)
  • Author(s): Hanna Cameron C.、Maxwell Joshua W. C.、Ismanto Hendra S.、Ashhurst Anneliese S.、Artner Lukas M.、Rudrawar Santosh、Britton Warwick J.、Yamasaki Sho、Payne Richard J.
  • Journal Title: Chemical Communications Volume: 58 Issue: 49 Pages: 6890-6893
  • DOI: 10.1039/d2cc02100e
  • Peer Reviewed
• [Journal Article] The intracellular pathogen <i>Francisella tularensis</i> escapes from adaptive immunity by metabolic adaptation (2022)
  • Author(s): Shibata Kensuke、Shimizu Takashi、Nakahara Mashio、Ito Emi、Legoux Francois、Fujii Shotaro、Yamada Yuka、Furutani-Seiki Makoto、Lantz Olivier、Yamasaki Sho、Watarai Masahisa、Shirai Mutsunori
  • Journal Title: Life Science Alliance Volume: 5 Issue: 10 Pages: e202201441-e202201441
  • DOI: 10.26508/lsa.202201441
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Trehalose diesters containing a polar functional group-modified lipid moiety: Synthesis and evaluation of Mincle-mediated signaling activity (2022)
  • Author(s): Matsumaru Takanori、Sueyoshi Kodai、Okubo Kana、Fujii Shusuke、Sakuratani Kasumi、Saito Ryota、Ueki Kazunari、Yamasaki Sho、Fujimoto Yukari
  • Journal Title: Bioorganic &amp; Medicinal Chemistry Volume: 75 Pages: 117045-117045
  • DOI: 10.1016/j.bmc.2022.117045
  • Peer Reviewed
• [Journal Article] Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b (2022)
  • Author(s): Shibata Kensuke、Motozono Chihiro、Nagae Masamichi、Shimizu Takashi、Ishikawa Eri、Motooka Daisuke、Okuzaki Daisuke、Izumi Yoshihiro、Takahashi Masatomo、Fujimori Nao、Wing James B.、Hayano Takahide、Asai Yoshiyuki、Bamba Takeshi、Ogawa Yoshihiro、Furutani-Seiki Makoto、Shirai Mutsunori、Yamasaki Sho
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 6948-6948
  • DOI: 10.1038/s41467-022-34802-8
  • Peer Reviewed / Open Access
• [Journal Article] 感染防御に寄与するT細胞の解析 (2022)
  • Author(s): 細野裕貴、山﨑晶
  • Journal Title: Precision Medicine 11月臨時増刊号 Volume: 5 Pages: 1-4
• [Journal Article] ゴーシェ病における神経細胞死誘導の新たな分子機構 (2022)
  • Author(s): 清水隆、山崎晶
  • Journal Title: 医学のあゆみ Volume: 283 Pages: 380-384
• [Journal Article] Self-referential immune recognition through C-type lectin receptors (2022)
  • Author(s): Guenther Carla、Nagae Masamichi、Yamasaki Sho
  • Journal Title: Adv. Immunol. Volume: 156 Pages: 1-23
  • DOI: 10.1016/bs.ai.2022.09.001
  • ISBN: 9780323989473
  • Peer Reviewed
• [Journal Article] Lectin recruits pathogenic bugs (2022)
  • Author(s): Schutt Charles R.、Yamasaki Sho
  • Journal Title: Journal of Experimental Medicine Volume: 220 Issue: 1
  • DOI: 10.1084/jem.20221732
• [Journal Article] Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant (2022)
  • Author(s): Mise-Omata, S., M. Ikeda, M. Takeshita, Y. Uwamino, M. Wakui, T. Arai, A. Yoshifuji, K. Murano, H. Siomi, K. Nakagawara, M. Ohyagi, M. Ando, N. Hasegawa, H. Saya, M. Murata, K. Fukunaga, H. Namkoong, X. Lu, S. Yamasaki, and A. Yoshimura.
  • Journal Title: J Immunol Volume: 209 Issue: 11 Pages: 2104-2113
  • DOI: 10.4049/jimmunol.2200525
  • Peer Reviewed / Open Access
• [Journal Article] Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2 (2022)
  • Author(s): Haji Shojiro、Ito Taiki、Guenther Carla、Nakano Miyako、Shimizu Takashi、Mori Daiki、Chiba Yasunori、Tanaka Masato、Mishra Sushil K、Willment Janet A、Brown Gordon D、Nagae Masamichi、Yamasaki Sho
  • Journal Title: eLife Volume: 11
  • DOI: 10.7554/elife.83037
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Water-soluble trehalose glycolipids show superior Mincle binding and signaling but impaired phagocytosis and IL-1β production (2022)
  • Author(s): Manthrirathna M. A. Thathsaranie P.、Dangerfield Emma M.、Ishizuka Shigenari、Woods Aodhamair、Luong Brenda S.、Yamasaki Sho、Timmer Mattie S. M.、Stocker Bridget L.
  • Journal Title: Frontiers in Molecular Biosciences Volume: 9 Pages: 1015210-1015210
  • DOI: 10.3389/fmolb.2022.1015210
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19 (2022)
  • Author(s): Ogura Hideki、Gohda Jin、Lu Xiuyuan、Yamamoto Mizuki、Takesue Yoshio、Son Aoi、Doi Sadayuki、Matsushita Kazuyuki、Isobe Fumitaka、Fukuda Yoshihiro、Huang Tai-Ping、Ueno Takamasa、Mambo Naomi、Murakami Hiromoto、Kawaguchi Yasushi、Inoue Jun-ichiro、Shirai Kunihiro、Yamasaki Sho、Hirata Jun-Ichi、Ishido Satoshi
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 7063-7063
  • DOI: 10.1038/s41467-022-34655-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C型レクチン受容体の多彩なリガンド認識機構の構造基盤 (2022)
  • Author(s): 長江雅倫、山崎晶
  • Journal Title: 基礎老化研究 Volume: 1 Pages: 3-9
• [Journal Article] Selective suppression of IL-10 transcription by calcineurin in dendritic cells through inactivation of CREB (2021)
  • Author(s): Lu Xiuyuan、Oh-hora Masatsugu、Takeda Kiyoshi、Yamasaki Sho
  • Journal Title: International Immunology Volume: 34 Issue: 4 Pages: 197-206
  • DOI: 10.1093/intimm/dxab112
  • Peer Reviewed
• [Journal Article] Kyushu and Okinawa Population Study (KOPS): a large prospective cohort study in Japan (2021)
  • Author(s): Ikezaki Hiroaki、Furusyo Norihiro、Nakashima Ryoko、Umemoto Makiko、Yamamoto Ken、Matsumoto Yuji、Ohta Azusa、Yamasaki Sho、Hiramine Satoshi、Takayama Koji、Ogawa Eiichi、Toyoda Kazuhiro、Murata Masayuki、Shimono Nobuyuki、Hayashi Jun
  • Journal Title: BMJ Open Volume: 11 Issue: 12 Pages: e053763-e053763
  • DOI: 10.1136/bmjopen-2021-053763
  • Peer Reviewed / Open Access
• [Journal Article] Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle (2021)
  • Author(s): Reijneveld Josephine F.、Holzheimer Mira、Young David C.、Lopez Kattya、Suliman Sara、Jimenez Judith、Calderon Roger、Lecca Leonid、Murray Megan B.、Ishikawa Eri、Yamasaki Sho、Minnaard Adriaan J.、Moody D. Branch、Van Rhijn Ildiko
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 2010-2010
  • DOI: 10.1038/s41598-021-81474-3
  • Peer Reviewed / Open Access
• [Journal Article] 【コロナウイルス感染の免疫学】SARS-CoV-2に対するT細胞免疫応答 (2021)
  • Author(s): 長江雅倫、細野裕貴、山崎晶
  • Journal Title: 炎症と免疫 Volume: 30 Pages: 28-32
• [Journal Article] （特集ワクチン設計のサイエンス）SARS-CoV-2特異的T細胞クロノタイプとエピトープ解析 (2021)
  • Author(s): 石塚茂宜、長江雅倫、山崎晶
  • Journal Title: 医学のあゆみ Volume: 279 Pages: 947-952
• [Journal Article] Immune discrimination of the environmental spectrum through C-type lectin receptors (2021)
  • Author(s): Torigoe Shota、Schutt Charles R、Yamasaki Sho
  • Journal Title: International Immunology Volume: 33 Issue: 12 Pages: 847-851
  • DOI: 10.1093/intimm/dxab074
  • Peer Reviewed
• [Journal Article] Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity (2021)
  • Author(s): Yamana Satoshi、Shibata Kensuke、Hasegawa Eiichi、Arima Mitsuru、Shimokawa Shotaro、Yawata Nobuyo、Takeda Atsunobu、Yamasaki Sho、Sonoda Koh-Hei
  • Journal Title: Mucosal Immunology Volume: 15 Issue: 2 Pages: 351-361
  • DOI: 10.1038/s41385-021-00469-5
  • Peer Reviewed
• [Journal Article] Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients (2021)
  • Author(s): Lu X, Hosono Y, Nagae M, Ishizuka S, Ishikawa E, Motooka D, Ozaki Y, Sax N, Maeda Y, Kato Y, Morita T, Shinnakasu R, Inoue T, Onodera T, Matsumura T, Shinkai M, Sato T, Nakamura S, Mori S, Kanda T, Nakayama EE, Shioda T, Kurosaki T, Takeda K, Kumanogoh A, Arase H, Nakagami H, Yamashita K, Takahashi Y, Yamasaki S.
  • Journal Title: J Exp Med. Volume: 218 Issue: 12
  • DOI: 10.1084/jem.20211327
  • Peer Reviewed / Open Access
• [Journal Article] Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells (2021)
  • Author(s): Kitai Yuki、Sato Ko、Tanno Daiki、Yuan Xiaoliang、Umeki Aya、Kasamatsu Jun、Kanno Emi、Tanno Hiromasa、Hara Hiromitsu、Yamasaki Sho、Saijo Shinobu、Iwakura Yoichiro、Ishii Keiko、Kawakami Kazuyoshi
  • Journal Title: Infection and Immunity Volume: 89 Issue: 10 Pages: 1-10
  • DOI: 10.1128/iai.00330-21
  • Peer Reviewed / Open Access
• [Journal Article] Selective expression of a C-type lectin receptor, Clec12b, on skin mast cells (2021)
  • Author(s): Iijima Ayana、Kanemaru Kazumasa、Wang Yaqiu、Nabekura Tsukasa、Nakamura Yoshiyuki、Fujisawa Yasuhiro、Mori Daiki、Ohmuraya Masaki、Yamasaki Sho、Tahara-Hanaoka Satoko、Shibuya Akira
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 561 Pages: 101-105
  • DOI: 10.1016/j.bbrc.2021.04.097
  • Peer Reviewed / Open Access
• [Journal Article] Trehalose diamide glycolipids augment antigen-specific antibody responses in a Mincle-dependent manner. (2021)
  • Author(s): Lynch, AT., Motozono, C., Foster, AJ., Kodar, K., Dangerfield, EM., Yamasaki, S., Wedlock, DN., Timmer, MSM., Stocker, BL.
  • Journal Title: Bioorg Chem. Volume: 110 Pages: 104747-104747
  • DOI: 10.1016/j.bioorg.2021.104747
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity (2021)
  • Author(s): Jonathan Trujillo-Viera, Rabih El-Merahbi, Vanessa Schmidt, Till Karwen, Angel Loza-Valdes, Akim Strohmeyer, Saskia Reuter, Minhee Noh, Magdalena Wit, Izabela Hawro, Sabine Mocek, Christina Fey, Alexander E Mayer, Mona C Loffler, Ilka Wilhelmi, Marco Metzger, Eri Ishikawa, Sho Yamasaki, Monika Rau, Andreas Geier et al.
  • Journal Title: EMBO Molecular Medicine Volume: 13 Issue: 5
  • DOI: 10.15252/emmm.202013548
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation. (2021)
  • Author(s): Iizasa, E., Chuma, Y., Uematsu, T., Kubota, M., Kawaguchi, H., Umemura, M., Toyonaga, K., Kiyohara, H., Yano, I., Colonna, M., Sugita, M., Matsuzaki, G., Yamasaki, S., Yoshida, H., Hara, H.
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 2299-2314
  • DOI: 10.1038/s41467-021-22620-3
  • NAID: 120007170570
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cholesteryl glucosides signal through the carbohydrate recognition domain of the macrophage inducible C-type lectin (mincle) (2021)
  • Author(s): Timmer Mattie S. M.、Teunissen Thomas J.、Kodar Kristel、Foster Amy J.、Yamasaki Sho、Stocker Bridget L.
  • Journal Title: Organic & Biomolecular Chemistry Volume: 19 Issue: 10 Pages: 2198-2202
  • DOI: 10.1039/d0ob02342f
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8+ T cells (2021)
  • Author(s): Shiga Masanobu、Miyazaki Jun、Tanuma Kozaburo、Nagumo Yoshiyuki、Yoshino Takayuki、Kandori Shuya、Negoro Hiromitsu、Kojima Takahiro、Tanaka Ryota、Okiyama Naoko、Fujisawa Yasuhiro、Watanabe Miyuki、Yamasaki Sho、Kiyohara Hideyasu、Watanabe Makoto、Sato Taka-aki、Tahara Hideaki、Nishiyama Hiroyuki、Yano Ikuya
  • Journal Title: Cancer Immunology, Immunotherapy Volume: - Issue: 9 Pages: 2529-2543
  • DOI: 10.1007/s00262-021-02870-2
  • Peer Reviewed
• [Journal Article] Helicobacter metabolites exacerbate gastritis through C-type lectin receptors. (2021)
  • Author(s): Nagata M, Toyonaga K, Ishikawa E, Haji S, Okahashi N, Takahashi M, Izumi Y, Imamura A, Takato K, Ishida H, Nagai S, Illarionov P, Stocker B L, Timmer M S M, Smith D G M, Williams S J, Bamba T, Miyamoto T, Arita M, Appelmelk B J, Yamasaki S*.
  • Journal Title: J. Exp. Med. Volume: 218(1) Issue: 1
  • DOI: 10.1084/jem.20200815
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Candida albicans steryl 6-O-acyl-α-d-mannosides agonize signalling through Mincle (2020)
  • Author(s): Nguyen Tram、Hosono Yuki、Shimizu Takashi、Yamasaki Sho、Williams Spencer J.
  • Journal Title: Chemical Communications Volume: 56 Issue: 95 Pages: 15060-15063
  • DOI: 10.1039/d0cc06263d
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Overexpression of Macrophage-Inducible C-Type Lectin Mincle Aggravates Proinflammatory Responses to Streptococcus pneumoniae with Fatal Outcome in Mice (2020)
  • Author(s): Hollwedel Femke D.、Maus Regina、Stolper Jennifer、Khan Ayesha、Stocker Bridget L.、Timmer Mattie S. M.、Lu Xiuyuan、Pich Andreas、Welte Tobias、Yamasaki Sho、Maus Ulrich A.
  • Journal Title: The Journal of Immunology Volume: 205 Issue: 12 Pages: 3390-3399
  • DOI: 10.4049/jimmunol.2000509
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cholesteryl 6-O-acyl-α-glucosides from diverse Helicobacter spp. signal through the C-type lectin receptor Mincle (2020)
  • Author(s): Smith Dylan G. M.、Ito Emi、Yamasaki Sho、Williams Spencer J.
  • Journal Title: Organic & Biomolecular Chemistry Volume: 18 Issue: 39 Pages: 7907-7915
  • DOI: 10.1039/d0ob01776k
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants (2020)
  • Author(s): Jin Shuyu、Vu Hue Thi、Hioki Kou、Noda Naotaka、Yoshida Hiroki、Shimane Toru、Ishizuka Shigenari、Takashima Ippei、Mizuhata Yoshiyuki、Beverly Pe Kathleen、Ogawa Tetsuya、Nishimura Naoya、Packwood Daniel、Tokitoh Norihiro、Kurata Hiroki、Yamasaki Sho、Ishii Ken J.、Uesugi Motonari
  • Journal Title: Angewandte Chemie International Edition Volume: 60 Issue: 2 Pages: 961-969
  • DOI: 10.1002/anie.202011604
  • NAID: 120006958092
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans (2020)
  • Author(s): Sato Y.、Sato K.、Yamamoto H.、Kasamatsu J.、Miyasaka T.、Tanno D.、Miyahara A.、Kagesawa T.、Oniyama A.、Kawamura K.、Yokoyama R.、Kitai Y.、Umeki A.、Ishizuka S.、Takano K.、Shiroma R.、Nakahata N.、Kawakami K.、Kanno E.、Tanno H.、Yamasaki S.、Hara H.、Ishii K.、Kawakami K.
  • Journal Title: Infection and Immunity Volume: 88 Issue: 11 Pages: 1-14
  • DOI: 10.1128/iai.00400-20
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury. (2020)
  • Author(s): Tanaka M, Saka-Tanaka M, Ochi K, Fujieda K, Sugiura Y, Miyamoto T, Kohda H, Ito A, Miyazawa T, Matsumoto A, Aoe S, Miyamoto Y, Tsuboi N, Maruyama S, Suematsu M, Yamasaki S, Ogawa Y, Suganami T.
  • Journal Title: J Exp Med. Volume: 217 Issue: 11
  • DOI: 10.1084/jem.20192230
  • Peer Reviewed / Open Access
• [Journal Article] Pivotal role of the carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro (2020)
  • Author(s): Nasu Junta、Uto Tomofumi、Fukaya Tomohiro、Takagi Hideaki、Fukui Takehito、Miyanaga Noriaki、Nishikawa Yotaro、Yamasaki Sho、Yamashita Yoshihiro、Sato Katsuaki
  • Journal Title: International Immunology Volume: 32 Issue: 10 Pages: 673-682
  • DOI: 10.1093/intimm/dxaa034
  • Peer Reviewed
• [Journal Article] The key entity of a DCAR agonist, phosphatidylinositol mannoside Ac1PIM1: its synthesis and immunomodulatory function (2020)
  • Author(s): Yohei Arai, Shota Torigoe, Takanori Matsumaru, Sho Yamasaki, Yukari Fujimoto
  • Journal Title: Org. Biomol. Chem. Volume: - Issue: 19 Pages: 3659-3663
  • DOI: 10.1039/c9ob02724f
  • Peer Reviewed / Open Access
• [Journal Article] Direct Binding Analysis Between C-Type Lectins and Glycans Using Immunoglobulin Receptor Fusion Proteins (2020)
  • Author(s): Watanabe Miyuki、Omahdi Zakaria、Yamasaki Sho
  • Journal Title: Methods Mol. Biol. Volume: 2132 Pages: 119-128
  • DOI: 10.1007/978-1-0716-0430-4_12
  • ISBN: 9781071604298, 9781071604304
  • Peer Reviewed
• [Journal Article] Recognition of Mycobacteria by Dendritic Cell Immunoactivating Receptor (2020)
  • Author(s): Toyonaga K, Yamasaki S.
  • Journal Title: Current topics in microbiology and immunology Volume: 429 Pages: 103-115
  • DOI: 10.1007/82_2020_203
  • ISBN: 9783030622367, 9783030622374
  • Peer Reviewed
• [Journal Article] Asymmetric Total Synthesis of Mycobacterial Diacyl Trehaloses Demonstrates a Role for Lipid Structure in Immunogenicity (2020)
  • Author(s): Holzheimer Mira、Reijneveld Josephine F.、Ramnarine Alexandrea K.、Misiakos Georgios、Young David C.、Ishikawa Eri、Cheng Tan-Yun、Yamasaki Sho、Moody D. Branch、Van Rhijn Ildiko、Minnaard Adriaan J.
  • Journal Title: ACS Chemical Biology Volume: 15 Issue: 7 Pages: 1835-1841
  • DOI: 10.1021/acschembio.0c00030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Agonistic or antagonistic mucosal-associated invariant T (MAIT) cell activity is determined by the 6-alkylamino substituent on uracil MR1 ligands (2020)
  • Author(s): Braganza Chriselle D.、Motozono Chihiro、Sonoda Koh-Hei、Yamasaki Sho、Shibata Kensuke、Timmer Mattie S. M.、Stocker Bridget L.
  • Journal Title: Chemical Communications Volume: in press Issue: 39 Pages: 529-5294
  • DOI: 10.1039/d0cc00247j
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Design of potent Mincle signalling agonists based on an alkyl β-glucoside template (2020)
  • Author(s): Smith Dylan G. M.、Hosono Yuki、Nagata Masahiro、Yamasaki Sho、Williams Spencer J.
  • Journal Title: Chemical Communications Volume: in press Issue: 31 Pages: 4292-4295
  • DOI: 10.1039/d0cc00670j
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice (2020)
  • Author(s): Zhang Shuya、Liu Huan、Yin Meimei、Pei Xiuying、Hausser Angelika、Ishikawa Eri、Yamasaki Sho、Jin Zheng Gen
  • Journal Title: Hepatology Volume: in press Issue: 5 Pages: 1717-1734
  • DOI: 10.1002/hep.31176
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Innate and acquired immune responses against mycobacterial lipids (2023)
  • Author(s): 山﨑 晶
  • Organizer: EID会議／日米合同パネル会議 U.S.-Japan Cooperative Medical Sciences Program
  • Int'l Joint Research / Invited
• [Presentation] A transient metabolite in Mycobacterium leprae PGL-I biosynthesis pathway is a potent PAMP (2023)
  • Author(s): Shigenari Ishizuka, J. Hessel M. van Dijk, Tomomi Kawakita, Yuji Miyamoto, Yumi Maeda, Masamichi Goto, Manabu Ato, Masamichi Nagae, Jeroen D. C. Codee, Sho Yamasaki
  • Organizer: EID会議／日米合同パネル会議 U.S.-Japan Cooperative Medical Sciences Program
  • Int'l Joint Research
• [Presentation] 抗酸菌に対する自然免疫と獲得免疫の共闘 (2023)
  • Author(s): 山﨑 晶
  • Organizer: 第96回日本細菌学会総会
  • Invited
• [Presentation] Recognition of internal/external metabolites via CLR and unconventional TCR (2023)
  • Author(s): 山﨑 晶
  • Organizer: メルボルン大学大阪大学合同シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 免疫受容体による病原体の識別と細胞応答決定機構 (2023)
  • Author(s): 山﨑 晶
  • Organizer: 「感染・免疫・がん・炎症」の拠点シンポジウム
  • Invited
• [Presentation] Innate Immune Sensing of Metabolites Causes Neuroinflammatory Diseases (2022)
  • Author(s): 山﨑晶
  • Organizer: JSICR/MMCB合同シンポジウム
  • Invited
• [Presentation] Helicobacter pyloriに対する免疫応答と胃炎誘導機構 (2022)
  • Author(s): 山﨑晶
  • Organizer: 第28回日本ヘリコバクター学会学術集会
  • Invited
• [Presentation] Novel antigen for mucosal-associated invariant T (MAIT) cells (2022)
  • Author(s): Emi Ito, Shinsuke Inuki, Yoshihiro Izumi, Masatomo Takahashi, Eri Ishikawa, Kensuke Shibata, Takeshi Bamba and Sho Yamasaki
  • Organizer: EMBO Workshop: CD1/MR1 restricted T lymphocytes
  • Int'l Joint Research
• [Presentation] MAIT細胞の新規脂質抗原の探索 (2022)
  • Author(s): 伊東瑛美、井貫晋輔、和泉自泰、高橋政友、石川絵里、柴田健輔、馬場健史、山﨑晶
  • Organizer: 第64回日本脂質生化学会
• [Presentation] グルコシルセラミドが誘導するグリア細胞異常に伴う神経細胞死とゴージェ病病態への寄与 (2022)
  • Author(s): 清水隆、Charles Schuut、山﨑晶
  • Organizer: 第30回日本Cell Death学会学術集会
• [Presentation] メタボロミクス技術を活用した新たなT細胞抗原の探索 (2022)
  • Author(s): 伊東瑛美、山﨑 晶
  • Organizer: 第16回メタボロームシンポジウム
  • Invited
• [Presentation] 感染に対する生体防御応答 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 第33回日本生体防御学会学術総会
  • Invited
• [Presentation] 糖質を介する免疫受容体による自己認識機構 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 第41回日本糖質学会年会
  • Invited
• [Presentation] レクチン受容体による結晶性物質の認識機構に関する構造基盤の解明 (2022)
  • Author(s): 長江雅倫、森正太郎、山﨑晶
  • Organizer: 第41回日本糖質学会年会
• [Presentation] 感染に対する免疫応答：SARS-CoV-2特異的Tfhクローンの同定と治療への展開 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 第10回Transplant Immunology Forum
  • Invited
• [Presentation] Host Defense (2022)
  • Author(s): 山﨑 晶
  • Organizer: 2022 UBC&OU Virtual Symposium on Infectious Diseases and Drug Development
  • Int'l Joint Research / Invited
• [Presentation] T cell responses against SARS-CoV-2 (2022)
  • Author(s): 山﨑 晶
  • Organizer: Web The 29th FAOBMB & 2022 CSBMB Conference
  • Int'l Joint Research / Invited
• [Presentation] Regulation of acquired immunity against SARS-CoV2 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 日独免疫ワークショップ
  • Int'l Joint Research / Invited
• [Presentation] Regulation of immune responses against infection (2022)
  • Author(s): 山﨑 晶
  • Organizer: BK4 2022 International Symposium on Frontiers in Biomedical Science
  • Int'l Joint Research / Invited
• [Presentation] 糖鎖を介する免疫受容体による自己認識機構 (2022)
  • Author(s): 山﨑 晶
  • Organizer: JCGGシンポジウム(第 19 回糖鎖科学コンソーシアム)
  • Invited
• [Presentation] 病原体を排除するからだのしくみ (2022)
  • Author(s): 山﨑 晶
  • Organizer: SpringX 超学校 CiDER(大阪大学感染症総合教育研究拠点)×ナレッジキャピタル 正しく学ぶ! 感染症から「いのち」と「くらし」を守る講座
  • Invited
• [Presentation] 感染における病原体脂質と免疫受容体の攻防 (2022)
  • Author(s): 山﨑 晶
  • Organizer: （公）微生物化学研究所講演会
  • Invited
• [Presentation] T cell responses against SARS-CoV-2 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Self-antigen for mucosal-associated invariant T (MAIT) cell (2022)
  • Author(s): Emi Ito, Ami Takeyama, Shotaro Mori, Kensuke Shibata, Eri Ishikawa, Masamichi Nagae and Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Identification of T cells responding to mycobacterial lipids (2022)
  • Author(s): Yuki Sakai, Xiuyuan Lu, Sho Yamasaki, Takashi Yoshiyama, Yoshihiko Hoshino
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Characterization of self glycolipids presented by CD1d that activate NKT cells (2022)
  • Author(s): Yuki Hosono, Noriyuki Tomiyasu, Yoshihiro Izumi, Akihiro Imamura, Eri Ishikawa, Atsushi Kumanogoh, Hideharu Ishida, Takeshi Bamba, Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Structural studies of public TCR against SARS-CoV-2 peptide clarified the broad spectrum of the clonotype (2022)
  • Author(s): Masamichi Nagae, Shotaro Mori, Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Direct activation of microglia by β-glucosylceramide exacerbates Gaucher disease (2022)
  • Author(s): Takashi Shimizu, Atsushi Kumanogoh, Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] Deciphering pathogen-specific T cell responses to a clonotype resolution (2022)
  • Author(s): Xiuyuan Lu, Yuki Hosono, Shigenari Ishizuka, Eri Ishikawa, Atsushi Kumanogoh, Yoshimasa Takahashi, Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
  • Invited
• [Presentation] Signal kinetics via common FcRγ chain generates distinct cellular responses by altering chromatin landscape (2022)
  • Author(s): Miyuki Watanabe, Sho Yamasaki
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] 免疫受容体を介する生理活性脂質の生体応答 (2022)
  • Author(s): 山﨑 晶
  • Organizer: 京都大学農学研究科 第12回公開シンポジウム
  • Invited
• [Presentation] 感染に対する免疫応答と疾患 (2022)
  • Author(s): 山﨑 晶
  • Organizer: Web 第46回協和キリン(慶應義塾大学)皮膚科免疫セミナー
  • Invited
• [Presentation] 感染に対する免疫応答と疾患 (2022)
  • Author(s): 山﨑 晶
  • Organizer: Web 大阪国際がんセンター研究所講演
  • Invited
• [Presentation] 感染に対する免疫応答と疾患 (2022)
  • Author(s): 山﨑 晶
  • Organizer: Web 第49回千葉基礎・臨床免疫セミナー
  • Invited
• [Presentation] シングルセルTCR解析を用いたSARS-CoV-2に対する獲得免疫応答の解析 (2021)
  • Author(s): 山崎 晶
  • Organizer: Web開催 10x Genomics - SONY サイエンスウェビナー
  • Invited
• [Presentation] Pathogenic conversion of host lipids by Helicobacter exacerbate gastritis through C-type lectin receptors (2021)
  • Author(s): 山崎 晶
  • Organizer: Web Cold Spring Harbor Asia Virtual meeting on Immunoreceptor Signalling: from Bench to Bed
  • Int'l Joint Research
• [Presentation] 感染に対する免疫応答と疾患 (2021)
  • Author(s): 山崎 晶
  • Organizer: Web【慶應医学部】第7回新次元開拓セミナー
  • Invited
• [Presentation] 特別講演「病原体を感知するからだのしくみ」 (2021)
  • Author(s): 山崎 晶
  • Organizer: Web開催 第1回 iGCORE(東海国立大学機構 糖鎖生命コア研究所) サイエンスカフェ 糖鎖って何？～「糖鎖、ゲノム、タンパク質」生命（いのち）を紡ぐ～
  • Invited
• [Presentation] MAIT細胞の新規生体由来リガンドの探索 (2021)
  • Author(s): 伊東瑛美、井貫晋輔、和泉自泰、高橋政友、石川絵里、馬場健史、山﨑晶
  • Organizer: Web開催 第63回 日本脂質生化学会
• [Presentation] P-37 Microglia activation by pathogenic metabolites exacerbates Gaucher disease (2021)
  • Author(s): 清水隆、熊ノ郷淳、山崎晶
  • Organizer: Web開催 MMCB 2020+1
• [Presentation] 糖鎖と免疫 (2021)
  • Author(s): 山﨑 晶
  • Organizer: Web Glycoforum講義
  • Invited
• [Presentation] 感染防御に寄与するT細胞クロノタイプの解析 (2021)
  • Author(s): 山﨑 晶
  • Organizer: Web 第32回日本生体防御学会学術集会
  • Invited
• [Presentation] 命を紡ぐ重要な機能～病原体を感知するからだのしくみ～ (2021)
  • Author(s): 山﨑 晶
  • Organizer: 第153回「つくば科学・技術産業イニシアティブ」セミナー
  • Invited
• [Presentation] Host immunity against mycobacterial infection (2021)
  • Author(s): 山﨑 晶
  • Organizer: ハイブリッド あわじ感染と免疫国際フォーラム
  • Int'l Joint Research / Invited
• [Presentation] Learning from mycobacteria to tackle pandemic (2021)
  • Author(s): 山﨑 晶
  • Organizer: ハイブリッド 第16回国際エンドトキシン・自然免疫学会
  • Int'l Joint Research / Invited
• [Presentation] スフィンゴ脂質蓄積による疾患と発症機構 (2021)
  • Author(s): 山﨑 晶
  • Organizer: 第94回日本生化学会
  • Invited
• [Presentation] Signal kinetics via common FcRγ chain generates distinct cellular responses by altering chromatin landscape (2021)
  • Author(s): Miyuki Watanabe, Sho Yamasaki
  • Organizer: 第５0回日本免疫学会学術集会
  • Invited
• [Presentation] Deciphering molecular link between kinases and transcription factors during iNKT cell development (2021)
  • Author(s): 石川 絵里、山﨑 晶
  • Organizer: 第５0回日本免疫学会学術集会
• [Presentation] ignal kinetics via common FcRγ chain generates distinct cellular responses by altering chromatin landscape (2021)
  • Author(s): 陸修遠、細野裕貴、石塚茂宜、石川絵里、熊ノ郷淳、高橋善正、山崎晶
  • Organizer: 第５0回日本免疫学会学術集会
• [Presentation] Direct activation of microglia by β-glucosylceramide exacerbates Gaucher disease (2021)
  • Author(s): 清水隆、熊ノ郷淳、山崎晶
  • Organizer: 第５0回日本免疫学会学術集会
• [Presentation] tructural studies of public TCR against SARS-CoV-2 peptide clarified the broad spectrum of the clonotype (2021)
  • Author(s): 長江雅倫、森正太郎、山崎晶
  • Organizer: 第５0回日本免疫学会学術集会
• [Presentation] 結核菌糖脂質アナログを活用する選択的T細胞活性化 (2021)
  • Author(s): 山﨑 晶
  • Organizer: Web 次世代アジュバント研究会
  • Invited
• [Presentation] 自然免疫T細胞による抗原認識と疾患 (2021)
  • Author(s): 山崎 晶
  • Organizer: Web開催 2020年度徳島大学先端酵素学研究所・共同利用共同研究拠点 成果報告会
  • Invited
• [Presentation] Helicobacter pyloriによる宿主脂質の病原因子への変換 (2021)
  • Author(s): 山崎 晶
  • Organizer: Web開催 第94回日本細菌学会総会シンポジウム
  • Invited
• [Presentation] 脂質認識免疫受容体を標的としたワクチンアジュバントの開発 (2020)
  • Author(s): 山崎 晶
  • Organizer: Web開催 第24回日本ワクチン学会シンポジウム
  • Invited
• [Presentation] Bacterial lipids promote deleterious inflammation through C-type lectin receptors (2020)
  • Author(s): 山崎 晶
  • Organizer: Web開催 千葉大学真菌医学研究センターMonthlyセミナー
  • Invited
• [Patent(Industrial Property Rights)] 神経型ゴーシェ病の予防・治療剤 (2022)
  • Inventor(s): 山﨑晶、清水隆
  • Industrial Property Rights Holder: 山﨑晶、清水隆
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-208678
  • Filing Date: 2022