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Functional analysis of heparin/heparan sulfate on regulation of B cell inhibitory receptor CD72

Research Project

Project/Area Number 17K17695
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
General medical chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

AKATSU Chizuru  東京医科歯科大学, 難治疾患研究所, 助教 (60735984)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords免疫学 / B細胞 / 自己免疫 / レクチン / CD72 / 硫酸化糖鎖
Outline of Final Research Achievements

CD72 is an inhibitory receptor mainly expressed in B cells and contains C-type lectin-like domain (CTLD) in its extracellular region. CD72 recognizes Sm/RNP, an SLE-related self antigen, through its CTLD and negatively regulates B cell response to Sm/RNP and inhibits SLE development. In this study, we revealed that CD72 recognizes various sulfated glycans besides Sm/RNP, and inhibits antibody production to the glycans. Furthermore, endocytosis of CD72 was regulated by the glycan ligands. These results suggested that inhibitory function of CD72 is regulated by its sulfated glycan ligands in B cells.

Academic Significance and Societal Importance of the Research Achievements

CD72はB細胞上に発現する抑制性の分子であり、日本での患者数が6-10万人と比較的有病率の高い自己免疫疾患であるSLEの発症を抑制する分子である。本研究によりCD72が硫酸化糖鎖を認識し、硫酸化糖鎖による機能制御を受けることが示唆されたことで、SLEの新たな治療法の開発に向けてCD72の機能を人為的に制御するための新たなターゲットが示された。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and (S)-Cetirizine by Lys191 in Human Histamine H1 Receptors.2018

    • Author(s)
      Hishinuma S, Tamura Y, Kobayashi C, Akatsu C, Shoji M
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 19 Issue: 12 Pages: 4067-75

    • DOI

      10.3390/ijms19124067

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 内因性糖鎖リガンドによるCD22/Siglec-2の機能制御2019

    • Author(s)
      Amin Alborzian Deh Sheikh, 赤津ちづる、鍔田武志
    • Organizer
      第5回糖鎖免疫研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The role of CD22 glycan cis-ligands in the regulation of B cell tonic signaling.2018

    • Author(s)
      Amin Alborzian Deh Sheikh, Chizuru Akatsu, Hideharu Ishida and Takeshi Tsubata
    • Organizer
      2018年度日本生化学会関東支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CD22の糖鎖リガンドはB細胞抗原受容体(BCR)の機能変化依存的にCD22のBCR抑制機能を制御する2018

    • Author(s)
      赤津ちづる、Alborzian-Deh-Sheikh Amin、石田秀治、鍔田武志
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] B細胞抑制性因子CD72とSm/RNPの複合体形成様式の推測2018

    • Author(s)
      沼本修孝, 赤津ちづる, 品川健朗, 鍔田武志, 伊藤暢聡
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of CD72 in the regulation of autoantibody production and type 1 interferon production in autoimmune disease2018

    • Author(s)
      Chizuru Akatsu, Quan-Zhen Li, and Takeshi Tsubata
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] SHP-1-activating B lymphocyte co-receptors and autoimmune diseases2018

    • Author(s)
      Chizuru Akatsu, Xuexin Li, Susumu Kusunoki, Takeshi Tsuabta
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Ligand recognition of the SHP-1-activating inhibitory B cell co-receptor CD722018

    • Author(s)
      Moe Endo, Chizuru Akatsu, Quan-Zhen Li, Chengsong Zhu, Teizo Fujita, Hideharu Sekine, Takeshi Tsubata
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery (ICPP13)
    • Related Report
      2018 Annual Research Report
  • [Presentation] SHP-1-activating B lymphocyte co-receptors and autoimmune diseases2018

    • Author(s)
      Chizuru Akatsu, Xuexin Li, Susumu Kusunoki, Takeshi Tsuabta
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery (ICPP13)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The role of ligand recognition of SHP-1 activating receptor CD22 in the regulation of B cell tonic signaling.2018

    • Author(s)
      Amin Alborzian Deh Sheikh, Chizuru Akatsu, Hideharu Ishida and Takeshi Tsubata
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery (ICPP13)
    • Related Report
      2018 Annual Research Report
  • [Presentation] SLE発症関連自己核酸抗原へのB細胞応答の新規抑制メカニズム2018

    • Author(s)
      赤津ちづる、鍔田武志
    • Organizer
      平成29年度新学術領域「ネオ・セルフ」若手の会
    • Related Report
      2017 Research-status Report
  • [Presentation] CD22糖鎖リガンドによるCD22の機能抑制2018

    • Author(s)
      赤津ちづる、Alborzian-Deh-Sheikh Amin、鍔田武志
    • Organizer
      糖鎖免疫研究会2018
    • Related Report
      2017 Research-status 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、赤津ちづる、品川健朗、劉志紅、Aslam Mohammad、鍔田武志、伊藤暢聡
    • Organizer
      第17回日本蛋白質科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cis-ligand dependent and independent interaction of receptor type protein tyrosine phosphatase CD45 with B cell inhibitory receptor CD222017

    • Author(s)
      Amin Alborzian-Deh-Sheikh, Chizuru Akatsu, Hideharu Ishida, and Takeshi Tsubata
    • Organizer
      平成29年度日本生化学会関東支部例会
    • Related Report
      2017 Research-status 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、沼本修孝、伊藤暢聡、鍔田武志
    • Organizer
      第32回自己免疫研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Charge distribution regulates the ligand-binding affinity of B cell inhibitory receptor CD722017

    • Author(s)
      Nobutaka Numoto, Chizuru Akatsu, Kenro Shinagawa, Takeshi Tsubata, and Nobutoshi Ito
    • Organizer
      第55回日本生物物理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] The Inhibitory B Cell Co-Receptor CD72 Regulates B Cell Response to Self Nucleic Acids Crucial for Development of SLE2017

    • Author(s)
      Chizuru Akatsu, Hongrui Yang, and Takeshi Tsubata
    • Organizer
      Korean Association of Immunologists (KAI) International Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of CD45 (PTPRC) in the regulation of SHP-1 (PTPN6)-activating receptor CD222017

    • Author(s)
      Chizuru Akatsu, Amin Alborzian-Deh-Sheikh, and Takeshi Tsubata
    • Organizer
      The 3rd Japan-Taiwan Bilateral Conference on Protein Phosphatase
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] CD45は糖鎖シスリガンドとしてCD22/Siglec-2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、Alborzian-Deh-Sheikh Amin、石田秀治、鍔田武志
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] CD72 recognizes RNA-related self-antigens and prevent autoimmunity2017

    • Author(s)
      Takeshi Tsubata, Hongrui Yang, and Chizuru Akatsu
    • Organizer
      第46回 日本免疫学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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