新たな病原体特異性を有するレクチン受容体ヘテロ二量体の戦略的探索

2014 Fiscal Year Annual Research Report

• Project/Area Number: 26670213
• Research Institution: Kyushu University
• Principal Investigator: 山崎 晶 九州大学, 生体防御医学研究所, 教授 (40312946)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: C型レクチン / 結核菌 / 自然免疫 / パターン認識受容体

Outline of Annual Research Achievements

結核菌のアジュバント活性を担うC型レクチン受容体Mincle（Clec4e）とMCL（Clec4d）がヘテロ二量体を形成し、相互に細胞表面発現を上昇させると共に、タンパク安定化を促すことで、リガンドに対する応答を著しく増強することを明らかにした。一般的にレクチン受容体はリガンド親和性が弱いため、同種受容体の凝集によって高野結合を形成し、avidityを増大させる仕組みが見受けられる。今回見出したヘテロ二量体は、親和性の低い受容体が、生物学的に意味のある結合力を確保する上での新たな戦略と考えられる。また、この異なるレクチン受容体によるヘテロ二量体の形成によって、認識する病原体の多様性も格段に広がり、病原体-宿主間の相互作用のメカニズムと生体応答がこれまで以上に明らかになっていくと期待される。

Research Products

• [Journal Article] C-Type lectin receptor MCL facilitates Mincle expression and signaling through complex formation. (2015)
  • Author(s): Miyake Y, Oh-Hora M, Yamasaki S.
  • Journal Title: J Immunol. Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Identification of pathogenic cardiac CD11c+ macrophages in Nod1-mediated acute coronary arteritis. (2015)
  • Author(s): Motomura Y, Kanno S, Asano K, Tanaka M, Hasegawa Y, Katagiri H, Saito T, Hara H, Nishio H, Hara T, Yamasaki S.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle. (2015)
  • Author(s): van der Peet PL, Gunawan C, Torigoe S, Yamasaki S, Williams SJ.
  • Journal Title: Chem Commun (Camb) Volume: 51 Pages: 5100-5103
  • DOI: 10.1039/c5cc00085h.
  • Peer Reviewed
• [Journal Article] The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity. (2015)
  • Author(s): Wilson GJ, Marakalala MJ, Hoving JC, van Laarhoven A, Drummond RA, Kerscher B, Keeton R, van de Vosse E, Ottenhoff TH, Plantinga TS, Alisjahbana B, Govender D, Besra GS, Netea MG, Reid DM, Willment JA, Jacobs M, Yamasaki S, van Crevel R, Brown GD.
  • Journal Title: Cell Host Microbe. Volume: 17 Pages: 252-259
  • DOI: 10.1016/j.chom.2015.01.004.
  • Peer Reviewed
• [Journal Article] Activation of an innate immune receptor, Nod1, accelerates atherogenesis in Apoe-/- mice. (2015)
  • Author(s): Kanno S, Nishio H, Tanaka T, Motomura Y, Murata K, Ihara K, Onimaru M, Yamasaki S, Kono H, Sueishi K, Hara T.
  • Journal Title: J Immunol. Volume: 194 Pages: 773-780
  • DOI: 10.4049/jimmunol.1302841.
  • Peer Reviewed
• [Journal Article] Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. (2015)
  • Author(s): Nakamura Y, Sato K, Yamamoto H, Matsumura K, Matsumoto I, Nomura T, Miyasaka T, Ishii K, Kanno E, Tachi M, Yamasaki S, Saijo S, Iwakura Y, Kawakami K.
  • Journal Title: Infect Immun. Volume: 83 Pages: 671-681
  • DOI: 10.1128/IAI.02835-14.
  • Peer Reviewed
• [Journal Article] Macrophage-inducible C-type lectin Mincle-expressing dendritic cells contribute to control of splenic Mycobacterium bovis BCG infection in mice. (2015)
  • Author(s): Behler F, Maus R, Bohling J, Knippenberg S, Kirchhof G, Nagata M, Jonigk D, Izykowski N, Mägel L, Welte T, Yamasaki S, Maus UA.
  • Journal Title: Infect Immun. Volume: 83 Pages: 184-196
  • DOI: 10.1128/IAI.02500-14.
  • Peer Reviewed
• [Journal Article] 3-O-sulfo-β-D-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5. (2015)
  • Author(s): Phongsisay V, Iizasa E, Hara H, Yamasaki S.
  • Journal Title: Mol Immunol. Volume: 63 Pages: 595-599
  • DOI: 10.1016/j.molimm.2014.07.023.
  • Peer Reviewed
• [Journal Article] Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. (2014)
  • Author(s): Tanaka M, Ikeda K, Suganami T, Komiya C, Ochi K, Shirakawa I, Hamaguchi M, Nishimura S, Manabe I, Matsuda T, Kimura K, Inoue H, Inagaki Y, Aoe S, Yamasaki S, Ogawa Y.
  • Journal Title: Nat Commun. Volume: 5 Pages: 4982
  • DOI: 10.1038/ncomms5982.
  • Peer Reviewed
• [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. (2014)
  • Author(s): Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
  • Journal Title: Immunity Volume: 41 Pages: 402-413
  • DOI: 10.1016/j.immuni.2014.08.005.
  • Peer Reviewed
• [Journal Article] Application of oocyte cryopreservation technology in TALEN-mediated mouse genome editing. (2014)
  • Author(s): Nakagawa Y, Sakuma T, Nakagata N, Yamasaki S, Takeda N, Ohmuraya M, Yamamoto T.
  • Journal Title: Exp Anim. Volume: 63 Pages: 349-355
  • Peer Reviewed
• [Journal Article] The tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) imposes a brake on antitumor activity of CD8 T cells. (2014)
  • Author(s): Giordano M, Roncagalli R, Bourdely P, Chasson L, Buferne M, Yamasaki S, Beyaert R, van Loo G, Auphan-Anezin N, Schmitt-Verhulst AM, Verdeil G.
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Pages: 11115-11120
  • DOI: 10.1073/pnas.1406259111.
  • Peer Reviewed
• [Journal Article] LMIR5 extracellular domain activates myeloid cells through toll-like receptor 4. (2014)
  • Author(s): Phongsisay V, Iizasa E, Hara H, Yamasaki S.
  • Journal Title: Mol Immunol. Volume: 62 Pages: 169-177
  • DOI: 10.1016/j.molimm.2014.06.012.
  • Peer Reviewed
• [Journal Article] Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage inducible C-type lectin, Mincle. (2014)
  • Author(s): Hattori Y, Morita D, Fujiwara N, Mori D, Nakamura T, Harashima H, Yamasaki S, Sugita M.
  • Journal Title: J Biol Chem. Volume: 289 Pages: 15405-15412
  • DOI: 10.1074/jbc.M114.566489.
  • Peer Reviewed
• [Journal Article] LAPTM5 promotes lysosomal degradation of intracellular CD3ζ but not of cell surface CD3ζ. (2014)
  • Author(s): Kawai Y, Ouchida R, Yamasaki S, Dragone L, Tsubata T, Wang JY.
  • Journal Title: Immunol Cell Biol. Volume: 92 Pages: 527-534
  • DOI: 10.1038/icb.2014.18.
  • Peer Reviewed
• [Journal Article] Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. (2014)
  • Author(s): Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, Kanduri K, Joly R, Malzac A, Lähdesmäki H, Lahesmaa R, Yamasaki S, Saito T, Malissen M, Aebersold, R, Gstaiger M, Malissen B.
  • Journal Title: Nat Immunol. Volume: 15 Pages: 384-392
  • DOI: 10.1038/ni.2843.
  • Peer Reviewed
• [Journal Article] Characterization of the receptors for mycobacterial cord factor in Guinea pig. (2014)
  • Author(s): Toyonaga K, Miyake Y, Yamasaki S.
  • Journal Title: PLoS One Volume: 9 Pages: e88747
  • DOI: 10.1371/journal.pone.0088747.
  • Peer Reviewed
• [Presentation] Regulation of immune responses through C-type lectin receptors (2015)
  • Author(s): Sho Yamasaki
  • Organizer: The 6th International Symposium of IFReC
  • Place of Presentation: 大阪
  • Year and Date: 2015-02-23 – 2015-02-24
  • Invited
• [Presentation] Recognition of fungal pathogens by C-type lectin receptors (2015)
  • Author(s): Sho Yamasaki
  • Organizer: Gordon Research Conferences 2015 Immunology of Fungal Infections
  • Place of Presentation: Galveston, USA
  • Year and Date: 2015-01-18 – 2015-01-23
  • Invited
• [Presentation] アジュバントの認識と免疫応答 (2014)
  • Author(s): 山崎 晶
  • Organizer: 第43回日本免疫学会学術集会アフィメトリクスランチョンセミナー
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] 損傷自己組織の認識と慢性炎症 (2014)
  • Author(s): 山崎 晶
  • Organizer: 第43回日本免疫学会学術集会オーバービュートーク
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] レクチン受容体による糖脂質認識と免疫応答 (2014)
  • Author(s): 山崎 晶
  • Organizer: 第12回日本糖鎖科学コンソーシアム（JCGG)シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] 結核菌を認識する受容体と免疫応答 (2014)
  • Author(s): 山崎 晶
  • Organizer: 感染症研究グローバルネットワークフォーラム2014
  • Place of Presentation: 千葉
  • Year and Date: 2014-11-15
  • Invited
• [Presentation] 細胞死に伴って放出される内因性アジュバントの同定 (2014)
  • Author(s): 山崎 晶
  • Organizer: 新学術領域研究「細胞死を起点とする生体制御ネットワークの解明」キックオフシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-11-13
• [Presentation] Recognition of mycobacterial adjuvants through C-type lectin receptors (2014)
  • Author(s): Sho Yamasaki
  • Organizer: 8th Vaccine and ISV Congress
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2014-10-26 – 2014-10-28
  • Invited
• [Presentation] Immune responses against glycolipids through C-type lectin receptors (2014)
  • Author(s): Sho Yamasaki
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] Immune regulation through C-type lectin receptors (2014)
  • Author(s): Sho Yamasaki
  • Organizer: Novo Nordisk Innovation Summit
  • Place of Presentation: 東京
  • Year and Date: 2014-10-01 – 2014-10-02
  • Invited
• [Presentation] Recognition of bacterial adjuvants through C-type lectin receptors. (2014)
  • Author(s): Sho Yamasaki
  • Organizer: 第13回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-23 – 2014-09-26
  • Invited
• [Presentation] Adjuvant recognition through C-type lectin Receptors. (2014)
  • Author(s): Sho Yamasaki
  • Organizer: 2014 Cold Spring Harbor Asia Conference on Frontiers of Immunology in Health and Diseases
  • Place of Presentation: Suzhou, China
  • Year and Date: 2014-09-02 – 2014-09-06
  • Invited
• [Presentation] Immune responses to pathogens through C-type lectin receptors. (2014)
  • Author(s): Sho Yamasaki
  • Organizer: International Symposium of the Institute Network
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-19 – 2014-06-20
  • Invited
• [Presentation] Adjuvant recognition through C-type lectin receptors. (2014)
  • Author(s): Sho Yamasaki
  • Organizer: The 22nd International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: 神戸
  • Year and Date: 2014-06-02 – 2014-06-03
  • Invited
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/labo/molimm/
• [Patent(Industrial Property Rights)] Adjuvant (2014)
  • Inventor(s): 山崎 晶
  • Industrial Property Rights Holder: 山崎 晶
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2014-173066
  • Filing Date: 2014-08-27