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Studies on Siglecs expressed on B lymphocytes and their glycan ligands

Research Project

Project/Area Number 26293062
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TSUBATA Takeshi  東京医科歯科大学, 難治疾患研究所, 教授 (80197756)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsシグレック / CD22 / Siglec-10 シスリガンド / CD45 / シアル酸 / シグナル伝達 / ギラン・バレー症候群 / シスリガンド / BCR / 糖鎖 / 免疫学 / Bリンパ球 / Siglec
Outline of Final Research Achievements

Siglecs expressed in various immune cells recognize sialic acids and mostly inhibit cell activation. In this study, we demonstrated that sialic acid-containing Siglec ligands expressed on the same cell (cis-ligands) can be efficiently labeled by proximity labeling. We elucidated how cis-ligands regulate Siglecs by analyzing CD45 that was isolated as a cis-ligand of CD22, a Siglec. Moreover, we demonstrated that the polymorphism of Siglec-10 associated with Guillain-Barre syndrome in which autoantibodies to gangliosides, sialic acid-containing glycolipids, are produced regulates binding of Siglec-10 to gangliosides. This result suggests that decreased activity of Siglec-10 allows immune responses to gangliosides, resulting in development of this syndrome.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (47 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (6 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 3 results) Presentation (30 results) (of which Int'l Joint Research: 2 results,  Invited: 13 results) Book (1 results)

  • [Int'l Joint Research] デューク大学/カリフォルニア大学サンタバーバラ校(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] マックスプランク研究所(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] デューク大学/カリフォルニア大学サンタバーバラ校(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マックスプランク研究所(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] デューク大学/カリフォルニア大学サンタバーバラ校(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] マックスプランク研究所(ドイツ )

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Negative regulation of B cell responses and self-tolerance to RNA-related lupus self-antigen2018

    • Author(s)
      Tsubata, T.
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 94 Issue: 1 Pages: 35-44

    • DOI

      10.2183/pjab.94.003

    • NAID

      130006307232

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proximity labeling of cis-ligands of CD22/Siglec-2 reveals stepwise α2,6 sialic acid-dependent and -independent interactions.2018

    • Author(s)
      Alborzian Deh Sheikh A, Akatsu C, Imamura A, Abdu-Allah HHM, Takematsu H, Ando H, Ishida H, Tsubata T
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 495 Issue: 1 Pages: 854-859

    • DOI

      10.1016/j.bbrc.2017.11.086

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD22-binding synthetic sialosides regulate B lymphocyte proliferation through CD22 ligand-dependent and independent pathways, and enhances antibody production in mice2018

    • Author(s)
      2.Matsubara N, Imamura A, Yonemiz Tu, Akatsu C, Yang H, Ueki A, Watanabe N, Abdu-Allah H, Numoto N, Takematsu H, Kitazume S, Tedder FT, Marth JD, Ito N, Ando H, Ishida H, Kiso M, and Tsubata T
    • Journal Title

      Frontiers in Immunology

      Volume: - Pages: 820-820

    • DOI

      10.3389/fimmu.2018.00820

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] B cell tolerance and autoimmunity2017

    • Author(s)
      Tsubata, T
    • Journal Title

      F1000Research

      Volume: 6 Pages: 391-391

    • DOI

      10.12688/f1000research.10583.1

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous Toll-like receptor 7 ligand Sm/RNP.2016

    • Author(s)
      Akatsu, C., Shinagawa, K., Numoto, N., Liu, Z., Konuscan, A.U., Aslam, M., Phoon, S., Adachi, T., Furukawa, K., Ito, N. and Tsubata. T.
    • Journal Title

      J. Exp. Med.

      Volume: 213 Issue: 12 Pages: 2691-2706

    • DOI

      10.1084/jem.20160560

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Ras GTPase-activating protein Rasal3 supports survival of naïve T cells.2015

    • Author(s)
      Muro R, Nitta T, Okada T, Ideta H, Tsubata T, Suzuki H
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0119898-e0119898

    • DOI

      10.1371/journal.pone.0119898

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] xcess CD40L does not rescue anti-DNA B cells from clonal anergy.2014

    • Author(s)
      Aslam, M., Kishi, Y. and Tsubata, T.
    • Journal Title

      F1000Research

      Volume: 2 Pages: 218-218

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional evaluation of activation-dependent alterations in the sialoglycan composition of T cells.2014

    • Author(s)
      Naito-Matsui Y, Takada S, Kano Y, Iyoda T, Sugai M, Shimizu A, Inaba K, Nitschke L, Tsubata T, Oka S, Kozutsumi Y, and Takematsu H.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 3 Pages: 1564-1579

    • DOI

      10.1074/jbc.m113.523753

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] FcmR interacts and cooperates with the B cell receptor to promote B cell survival.2014

    • Author(s)
      Ouchida. R., Lu. Q., Liu. J., Li. Y., Chu. Y., Tsubata. T. and Wang, J.Y.
    • Journal Title

      J. Immunol.

      Volume: 194 Issue: 7 Pages: 3096-4101

    • DOI

      10.4049/jimmunol.1402352

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] CD22糖鎖リガンドによるCD22の機能制御2018

    • Author(s)
      鍔田武志
    • Organizer
      糖鎖免疫研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] シスリガンドによる CD22 の制御2017

    • Author(s)
      鍔田武志
    • Organizer
      糖鎖免疫研究会
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2017-01-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Cis-ligand dependent and independent interaction of receptor type protein tyrosine phosphatase CD45 with B cell inhibitory receptor CD22.2017

    • Author(s)
      Amin Alborzian-Deh-Sheikh
    • Organizer
      The Regular Meeting of the Japanese Biochemical Society, Kanto Branch 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 結晶構造によるB細胞 抑制性因子CD72のリガンド結合部位の推測.2017

    • Author(s)
      沼本修孝
    • Organizer
      第17回日本蛋白質科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抑制性受容体CD72によるRNA関連自己抗原への自己免 疫応答の制御2017

    • Author(s)
      赤津 ちづる
    • Organizer
      第32回自己免疫研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Charge distribution regulates the ligand-binding affinity of B cell inhibitory receptor CD722017

    • Author(s)
      Nobutaka Numoto
    • Organizer
      The 55th Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2017 Annual Research Report
  • [Presentation] The Inhibitory B Cell Co-Receptor CD72 Regulates B Cell Response to Self Nucleic Acids Crucial for Development of SLE.2017

    • Author(s)
      Takeshi Tsubata
    • Organizer
      Korean Association of Immunologists (KAI) International Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] RoleofCD45(PTPRC)intheregulation of SHP-1 (PTPN6)-activating receptor CD22.2017

    • Author(s)
      TakeshiTsubata
    • Organizer
      The 3rd Japan-Taiwan Bilateral Conference on Protein Phosphatase
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CD45は糖鎖シスリガンドとしてCD22/Siglec2を抑制することでBリンパ球分化を促進する.2017

    • Author(s)
      赤津ちづる
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CD72recognizesRNA-relatedself-antigensandprevents autoimmunity.2017

    • Author(s)
      TakeshiTsubata
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] シスリガンドによる CD22 の制御2017

    • Author(s)
      鍔田 武志
    • Organizer
      糖鎖免疫研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] シアル酸合成展開による免疫応答制御化合物の開発2016

    • Author(s)
      松原直子
    • Organizer
      日本ケミカルバイオロジー学会第11回年会
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] 糖鎖抗原への免疫応答・不応答のメカニズム2015

    • Author(s)
      鍔田武志
    • Organizer
      共同研究拠点研究集会 Glyco Immunology 2014.
    • Place of Presentation
      東京医科歯科大学、東京
    • Year and Date
      2015-02-17 – 2015-02-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD22/Siglec2の糖鎖リガンドの機能とBリンパ球活性化制御2015

    • Author(s)
      松原直子、安藤弘宗、今村彰宏、菅沼勇輝、竹松弘、石田秀治、木曽真、鍔田武志
    • Organizer
      共同研究拠点研究集会 Glyco Immunology 2014.
    • Place of Presentation
      東京医科歯科大学、東京
    • Year and Date
      2015-02-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] A mouse model for chronic inflammatory diseases spontaneously develops CD4/CD8 double-positive T cell leukemia/lymphoma.2015

    • Author(s)
      P. A. Koni., Ren, M., Tsubata, T., Khleif, S., Maverakis, E. and Shimoda, M.
    • Organizer
      The 54th Midwinter Conference of Immunologists at Asilomar.
    • Place of Presentation
      Big Bear Lake, California (USA)
    • Year and Date
      2015-01-24 – 2015-01-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Bリンパ球に発現するCD22/Siglec-2を標的とした免疫増強化合物の開発2015

    • Author(s)
      鍔田武志
    • Organizer
      第8回次世代アジュバント研究会
    • Place of Presentation
      千里ライフサイエンスセンター、大阪
    • Year and Date
      2015-01-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD273+memory B cells replenish bone marrow plasma cells in the steady state after influenza vaccination.2014

    • Author(s)
      Onodera, T., Adachi, T., Tsubata, T., Kurosaki, T., Adachi, Y., Ato, M., Takahashi, Y.
    • Organizer
      Annual Meeting of the Japanese Society for Immunology, 2014.
    • Place of Presentation
      京都国際会館、Kyoto
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthetic sialosides that bind to CD22 with nanomolar potency activate B lymphocytes.2014

    • Author(s)
      Matsubara, N., Takematsu, H. and Tsubata, T.
    • Organizer
      Annual Meeting of the Japanese Society for Immunology, 2014.
    • Place of Presentation
      京都国際会館、Kyoto
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] The Role of Reactive Oxygen Species in B Cell Antigen Receptor Signaling.2014

    • Author(s)
      Tang, M., Takata, T., Suzuki, M. and Tsubata, T.
    • Organizer
      Annual Meeting of the Japanese Society for Immunology, 2014.
    • Place of Presentation
      京都国際会館、Kyoto
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Real3, a newly identified Ras GTPase activating protein is important for survival of naïve T cells in the periphery.2014

    • Author(s)
      Muro, R., Nitta, T., Okada, T., and Tsubata, T.
    • Organizer
      Annual Meeting of the Japanese Society for Immunology, 2014.
    • Place of Presentation
      京都国際会館、Kyoto
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] CD22-binding synthetic sialosides as a tool to elucidate the role of CD22 cis-ligand and as a novel immunostimulan.2014

    • Author(s)
      Tsubata, T.
    • Organizer
      Medical Research Institute 40th Anniversary, 13th Surugadai International Symposium & Joint Usage/Research Program of Medical Research Institute International Symposium.
    • Place of Presentation
      Tokyou Medical and Dental Univ. Tokyo
    • Year and Date
      2014-11-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Role of CD22/Siglec2 and its ligand in B lymphocyte activation.2014

    • Author(s)
      Tsubata, T.
    • Organizer
      Joint annual meeting of SFG &JSCR, Integrating Glycoscience from Biology and Chemistry to Medicine.
    • Place of Presentation
      Hilton Hawaiian Village, Honolulu, Hawaii (USA)
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Synthetic sialosides that regulate CD22/Siglec-2, a B lymphocyte membrane molecule activating SH2-containing phosphatases.2014

    • Author(s)
      Tsubata, T.
    • Organizer
      11th International Conference on Protein Phosphatase
    • Place of Presentation
      Tohoku Univ. Sendai, Japan
    • Year and Date
      2014-11-12 – 2014-11-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 免疫グロブリンの機能多様性と疾患2014

    • Author(s)
      鍔田武志
    • Organizer
      第三回高齢者ネフローゼ症候群治療研究会・講演会
    • Place of Presentation
      KPP八重洲ビル、東京
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 近畿圏を中心としたリウマチ膠原病専門医2014

    • Author(s)
      鍔田武志
    • Organizer
      臨床免疫セミナー
    • Place of Presentation
      ウエスティン都ホテル、京都
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] B細胞共受容体CD72のC型レクチン様ドメインのX線結晶構造解析2014

    • Author(s)
      品川健朗、沼本修好、鍔田武志、伊藤暢聡
    • Organizer
      第52回日本生物物理学会
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Bリンパ球の活性化制御と自己免疫2014

    • Author(s)
      鍔田武志
    • Organizer
      第23回日本シェーグレン症候群学会学術集会
    • Place of Presentation
      ホテルニュー長崎、長崎
    • Year and Date
      2014-09-12 – 2014-09-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 自己反応性Bリンパ球の制御と細胞死2014

    • Author(s)
      鍔田武志
    • Organizer
      第23回日本Cell Deth学会学術集会
    • Place of Presentation
      東京医科歯科大学、東京
    • Year and Date
      2014-07-18 – 2014-07-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] B細胞受容体(BCR)シグナル応答におけるROS産生とその役割2014

    • Author(s)
      鈴木光浩、唐淼、高田俊太朗、焦旭阳、鍔田武志
    • Organizer
      生化学学会関東地方会
    • Place of Presentation
      茨城大学、茨城
    • Year and Date
      2014-07-18 – 2014-07-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] SLE関連自己反応性B細胞のトレランスとその破綻: Distinct tolerance mechanisms for anti-DNA and anti-Sm B cells.2014

    • Author(s)
      Mohammad, A., Kishi Y., Weigert, M. G. and Tsubata, T.
    • Organizer
      第29回自己免疫研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-12
    • Related Report
      2014 Annual Research Report
  • [Book] Siglecs and B cell regulation.In: Taniguchi N., Endo T., Hart G., Seeberger P., Wong C. (Ed.) Glycoscience: Biology and Medicine: SpringerReference (www.springerreference.com)..2014

    • Author(s)
      Tsubata, T.
    • Total Pages
      400
    • Publisher
      Springer-Verlag Berlin Heidelberg
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2022-02-21  

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