Analyses on the heterodimer formation between different C-type lectin receptors

• Project/Area Number: 26670213
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Kyushu University
• Principal Investigator: YAMASAKI Sho 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• 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 Final Research Achievements

In this study, we demonstrate that MCL interacts with Mincle to promote its surface expression. After LPS or zymosan stimulation, MCL-deficient bone marrow-derived dendritic cells (BMDCs) had a lower level of Mincle protein expression. Meanwhile, BMDCs from MCL transgenic mice showed an enhanced level of Mincle expression on the cell surface. MCL was associated with Mincle through the stalk region and this region was necessary and sufficient for the enhancement of Mincle expression. This interaction appeared to be mediated by the hydrophobic repeat of MCL, as substitution of four hydrophobic residues within the stalk region with serine (MCL(4S)) abolished the function to enhance the surface expression of Mincle. MCL(4S) mutant failed to restore the defective TDM responses in MCL-deficient BMDCs. These results suggest that MCL positively regulates Mincle expression through protein-protein interaction via its stalk region, thereby magnifying Mincle-mediated signaling.

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
  • 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
  • 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 Issue: 24 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 Issue: 2 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 Issue: 2 Pages: 773-780
  • DOI: 10.4049/jimmunol.1302841
  • Peer Reviewed / Open Access
• [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 Issue: 2 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): Friederike Behler, Regina Maus, Jennifer Bohling, Sarah Knippenberg, Gabriele Kirchhof, Masahiro Nagata, Danny Jonigk, Nicole Izykowski, Lavinia Mägel, Tobias Welte, Sho Yamasaki, Ulrich A. Maus
  • Journal Title: Infection and Immunity Volume: 83 Issue: 1 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: Molecular Immunology Volume: 63 Issue: 2 Pages: 595-595
  • 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, et al.
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 4982-4982
  • DOI: 10.1038/ncomms5982
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Issue: 3 Pages: 402-13
  • DOI: 10.1016/j.immuni.2014.08.005
  • Peer Reviewed / Open Access
• [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 Issue: 30 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: Molecular Immunology Volume: 62 Issue: 1 Pages: 169-169
  • 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: The Journal of Biological Chemistry Volume: 289(22) Issue: 22 Pages: 15405-12
  • DOI: 10.1074/jbc.m114.566489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] LAPTM5 promotes lysosomal degradation of intracellular but not the cell surface CD3ζimmunol.. (2014)
  • Author(s): Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T. and Wang, J.-Y.
  • Journal Title: Cell Biol. Volume: 92 Issue: 6 Pages: 527-534
  • DOI: 10.1038/icb.2014.18
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantitative proteomic analysis of signalsome dynamics in primary T cells identifies the CD6 surface receptor as a LAT-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., Lahdesmaki H., Lahesmaa R., Yamasaki S., Saito T., Malissen M., Aebersold R., Gstaiger M., and Malissen B.
  • Journal Title: Nat. Immunol. Volume: 15 Issue: 4 Pages: 384-392
  • DOI: 10.1038/ni.2843
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Issue: 2 Pages: e88747-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: 2014-173066
  • Filing Date: 2014-08-27