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Dual roles of type I interferon-activated B cells and the effect on autoimmunity

Research Project

Project/Area Number 18H02626
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionKyushu University

Principal Investigator

Baba Yoshihiro  九州大学, 生体防御医学研究所, 教授 (20415269)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsB細胞 / インターフェロン / IL-10 / 自己免疫疾患 / 制御性B細胞 / I型インターフェロン
Outline of Final Research Achievements

Although type I interferon (IFN-I) is known to have the dual role of exacerbation and suppression of autoimmune diseases, its underlying molecular mechanism remain unclear. In this study, we addressed the issue by examining the B cell response to IFN-I. We showed that human B cells give rise to IL-10-producing plasmablasts by stimulating IFN-I, and revealed its properties. Furthermore, we found that the IL-10 plasmablasts inhibit T cell proliferation. We also showed that murine B cells respond to TLR agonists and IFN-I synergistically and cooperately to differentiate into IL-10-producing and non-producing plasmablasts.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を迎えた先進国では自己免疫患者数の増加が大きな問題となっているが、その発症原因は不明であり、治療法も限定的である。制御性B細胞の分化がIFNで誘導されるという知見は、自己免疫疾患を抑制するB細胞を増幅させて治療に用いる方法に重要な情報となると考えられる。また、TLRアゴニストとIFN-Iのクロストークにより、自己免疫を増悪する抗体産生プラズマブラストから抑制するプラズマブラストへ分化の方向性を制御する可能性を示唆しており、プラズマ細胞分化の新規分子機構となることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (11 results) (of which Invited: 8 results) Book (2 results)

  • [Journal Article] Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells.2021

    • Author(s)
      Yasuda T, Saito Y, Ono C, Kawata K, Baba A, Baba Y.
    • Journal Title

      Sci. Rep.

      Volume: 11 Issue: 1 Pages: 5524-5524

    • DOI

      10.1038/s41598-021-84786-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity2020

    • Author(s)
      Tanaka, S. Ise, W. Inoue, T. Ito, A. Ono, C. Shima, Y. Sakakibara, S. Nakayama, M. Fujii, K. Miura, I. Sharif, J. Koseki, H. Koni, P. A. Raman, I. Li, Q. Z. Kubo, M. Fujiki, K. Nakato, R. Shirahige, K. Araki, H. Miura, F. Ito, T. Kawakami, E. Baba, Y. Kurosaki, T.
    • Journal Title

      Nature Immunology

      Volume: 21 Issue: 8 Pages: 950-961

    • DOI

      10.1038/s41590-020-0700-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes2020

    • Author(s)
      Sakaguchi Taiki、Okumura Ryu、Ono Chisato、Okuzaki Daisuke、Kawai Takafumi、Okochi Yoshifumi、Tanimura Natsuko、Murakami Mari、Kayama Hisako、Umemoto Eiji、Kioka Hidetaka、Ohtani Tomohito、Sakata Yasushi、Miyake Kensuke、Okamura Yasushi、Baba Yoshihiro、Takeda Kiyoshi
    • Journal Title

      Cell Reports

      Volume: 31 Issue: 10 Pages: 107755-107755

    • DOI

      10.1016/j.celrep.2020.107755

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] B Cell Receptor Signaling.2020

    • Author(s)
      Tanaka S, Baba Y.
    • Journal Title

      Adv. Exp. Med. Biol.

      Volume: 1254 Pages: 23-36

    • DOI

      10.1007/978-981-15-3532-1_2

    • ISBN
      9789811535314, 9789811535321
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Heterogeneous subsets of B-lineage regulatory cells (Breg cells).2020

    • Author(s)
      Baba Y, Saito Y, Kotetsu Y.
    • Journal Title

      Int. Immunol.

      Volume: 32 Issue: 3 Pages: 155-16

    • DOI

      10.1093/intimm/dxz068

    • Related Report
      2020 Annual Research Report
  • [Journal Article] GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells2019

    • Author(s)
      Usui R, Yabe D, Fauzi M, Goto H, Botagarova A, Tokumoto S, Tatsuoka H, Tahara Y, Kobayashi S, Manebe T, Baba Y, Kurosaki T, Herrera PL, Ogura M, Nagashima K, Inagaki N
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 15562-15562

    • DOI

      10.1038/s41598-019-52048-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors2019

    • Author(s)
      Nakai Akiko、Fujimoto Jun、Miyata Haruhiko、Stumm Ralf、Narazaki Masashi、Schulz Stefan、Baba Yoshihiro、Kumanogoh Atsushi、Suzuki Kazuhiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 7 Pages: 1630-1647

    • DOI

      10.1084/jem.20181494

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] THE ROLL OF B CELLS IN ALLERGY2019

    • Author(s)
      齋藤雄一、馬場義裕
    • Journal Title

      Japanese Journal of Allergology

      Volume: 68 Issue: 6 Pages: 661-667

    • DOI

      10.15036/arerugi.68.661

    • NAID

      130007678533

    • ISSN
      0021-4884, 1347-7935
    • Related Report
      2019 Annual Research Report
  • [Journal Article] The COMMD3/8 complex is a determinant of GRK6 specificity for chemoattractant receptors.2019

    • Author(s)
      Nakai A, Fujimoto J, Haruhiko M, Stumm R, Narazaki M, Schulz S, Baba Y, Kumanogoh A, Suzuki K.
    • Journal Title

      J. Exp. Med.

      Volume: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitive detection of fluorescence in western blotting by merging images2018

    • Author(s)
      Kondo Yukari、Higa Shinichiro、Iwasaki Takeshi、Matsumoto Tomoya、Maehara Kazumitsu、Harada Akihito、Baba Yoshihiro、Fujita Masatoshi、Ohkawa Yasuyuki
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 1 Pages: 0191532-0191532

    • DOI

      10.1371/journal.pone.0191532

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] B細胞の免疫応答制御機構2020

    • Author(s)
      馬場義裕
    • Organizer
      第16回皮膚免疫疾患研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] B細胞による自己免疫疾患制御2020

    • Author(s)
      馬場義裕
    • Organizer
      免疫と神経疾患オンラインセミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] B細胞はどのようにして免疫応答を制御するのか2019

    • Author(s)
      馬場義裕
    • Organizer
      第93回染色体工学研究センターセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] B細胞の免疫応答制御機構2019

    • Author(s)
      馬場義裕
    • Organizer
      がん免疫セミナー(千葉)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] B細胞の免疫応答制御機構2019

    • Author(s)
      馬場義裕
    • Organizer
      がん免疫セミナー(東京)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 免疫反応を抑制するB細胞2019

    • Author(s)
      馬場義裕
    • Organizer
      第18回レジェンドセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Role of Fcrl5 in B cell immune response and peripheral tolerance2019

    • Author(s)
      Ono C, Kochi Y, Tanaka S, Yamamoto K, Baba Y.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Ten-eleven translocaion (Tet) in B cells prevent autoimmunity2019

    • Author(s)
      Tanaka S, Ise W, Kurosaki T, Baba Y.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of IL-17A+ Vγ6γδ T cells in mouse thymus2019

    • Author(s)
      Hatano S, Tun X, Matsumoto M, Baba Y, Yoshikai Y.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Humoral immunity and diseases2018

    • Author(s)
      馬場義裕
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] B細胞による炎症制御機構2018

    • Author(s)
      馬場義裕
    • Organizer
      第 9 回中国免疫不全症研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 「B細胞分化」標準免疫学2021

    • Author(s)
      馬場義裕
    • Total Pages
      9
    • Publisher
      医学書院
    • ISBN
      9784260042383
    • Related Report
      2020 Annual Research Report
  • [Book] 制御性B細胞と疾患2018

    • Author(s)
      川上亮、馬場義裕
    • Publisher
      先端医学社 炎症と免疫
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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