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Role of cytokine-producing effector B cells in autoimmune diseases

Research Project

Project/Area Number 18K08410
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionKyushu University

Principal Investigator

NIIRO HIROAKI  九州大学, 医学研究院, 教授 (20380636)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords自己免疫疾患 / B細胞 / 免疫学 / 内科
Outline of Final Research Achievements

The clinical efficacy of B cell-targeted therapy for autoimmune diseases has gained attention to the antibody-independent functions of B cells, particularly their ability to produce cytokines. In this study we identified novel memory B cell subsets that produce GM-CSF, CXCL9/10, and IFNγ,and elucidated the differentiation induction mechanisms and their roles in the pathogenesis of autoimmune diseases.

Academic Significance and Societal Importance of the Research Achievements

近年の研究から、B細胞には病原性ならびに制御性サブセットの両方が存在することが明らかとなった。自己免疫疾患に対する現在のB細胞標的療法は、これら両方のサブセットを無差別に標的とするものである。本研究で得られた知見は、本疾患における病原性サブセットのみを標的とした理想的B細胞標的療法の開発につながる可能性がある。

Report

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

    (24 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Type 1 helper T cells generate CXCL9/10-producing T-bet + effector B cells potentially involved in the pathogenesis of rheumatoid arthritis2021

    • Author(s)
      Nakayama T, Yoshimura M, Higashioka K, Miyawaki K, Ota Y, Ayano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Kikukawa M, Yamada H, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Cell Immunol.

      Volume: 360 Pages: 104263-104263

    • DOI

      10.1016/j.cellimm.2020.104263

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of circulating SLAMF7+Tfh1 cells with IgG4 levels in patients with IgG4-related disease.2020

    • Author(s)
      Higashioka K, Ota Y, Maehara T, et. al.
    • Journal Title

      BMC Immunol.

      Volume: 21 Issue: 1 Pages: 31-31

    • DOI

      10.1186/s12865-020-00361-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a novel CD30 + B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis2020

    • Author(s)
      Higashioka K, Kikushige Y, Ayano M, Kimoto Y, Mitoma H, Kikukawa M, Akahoshi M, Arinobu Y, Horiuchi T, Akashi K, Niiro H.
    • Journal Title

      Clin Exp Immunol.

      Volume: 201 Issue: 3 Pages: 233-243

    • DOI

      10.1111/cei.13477

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD34-selected versus unmanipulated autologous hematopoietic stem cell transplantation in the treatment of severe systemic sclerosis: a post hoc analysis of a phase I/II clinical trial conducted in Japan.2019

    • Author(s)
      Ayano M, Tsukamoto H, Mitoma H, Kimoto Y, Akahoshi M, Arinobu Y, Miyamoto T, Horiuchi T, Niiro H, Nagafuji K, Harada M, Akashi K
    • Journal Title

      Arthritis Res Ther.

      Volume: 21 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s13075-019-1823-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines2019

    • Author(s)
      Takaki-Kuwahara Ayako、Arinobu Yojiro、Miyawaki Kohta、Yamada Hisakata、Tsuzuki Hirofumi、Irino Kensuke、Ayano Masahiro、Kimoto Yasutaka、Mitoma Hiroki、Akahoshi Mitsuteru、Tsukamoto Hiroshi、Horiuchi Takahiko、Niiro Hiroaki、Akashi Koichi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 198-198

    • DOI

      10.1186/s13075-019-1984-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term efficacy of infliximab treatment and the predictors of treatment outcomes in patients with refractory uveitis associated with Behcet’s disease.2018

    • Author(s)
      (1)Ueda S, Akahoshi M, Takeda A, Inoue Y, Omoto A, Ayano M, Kimoto Y, Mitoma H, Arinobu Y, Niiro H, Tsukamoto H, Horiuchi T, Hikita SI, Fukuhara T, Ishibashi T, Sonoda KH, Akashi K
    • Journal Title

      Eur J Rheumatol

      Volume: 5 Issue: 1 Pages: 9-15

    • DOI

      10.5152/eurjrheum.2017.17068

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study2018

    • Author(s)
      (2)Otsuka Y, Kiyohara C, Kashiwado Y, Sawabe T, Nagano S, Kimoto Y, Ayano M, Mitoma H, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T
    • Journal Title

      PLoS One

      Volume: 13 Issue: 4 Pages: e0196368-e0196368

    • DOI

      10.1371/journal.pone.0196368

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of central/effector memory T cells and Th1 polarization in malignant melanoma patients treated with anti-PD-1 antibody.2018

    • Author(s)
      (3)Yamaguchi K, Mishima K, Ohmura H, Hanamura F, Ito M, Nakano M, Tsuchihashi K, Ota SI, Wada N, Uchi H, Ariyama H, Kusaba H, Niiro H, Akashi K, Baba E
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 10 Pages: 3032-3042

    • DOI

      10.1111/cas.13758

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 実臨床におけるベリムマブ使用下でのSLE患者の臨床経過の検討2020

    • Author(s)
      吉村 元樹、三嶋 耕司、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、有信 洋二郎、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肺病変・慢性感染症合併の関節リウマチ患者における生物学的製剤の使用2020

    • Author(s)
      吉村 元樹、三嶋 耕司、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、有信 洋二郎、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A novel IL-21-producing CD8+ T cell subset involved in the pathogenesis of rheumatoid arthritis2019

    • Author(s)
      Kazuhiko Higashioka, Hiroaki Niiro
    • Organizer
      Keystone Symposia B Cell-T Cell Interactions
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activation of caspase-1 in CD16-positive monocyte and correlation with disease activity in systemeic lupus erythmatosus2019

    • Author(s)
      Shoichiro Inokuchi, Hiroki Mitoma, Shotaro Kawano, Masahiro Ayano, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pathologic role of activated SLAMF7+Tfh1 cells in facilitating IgG4 production by B cells in IgG4-related disease2019

    • Author(s)
      Kazuhiko Higashioka, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Tumor Necrosis Factor Receptor 2 Signaling Potentiates Proliferation and Suppressive Activities of Follicular Regulatory T Cells2019

    • Author(s)
      Shotaro Kawano, Hiroki Mitoma, Shoichiro Inokuchi, Masahiro Ayano, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi and Hiroaki Niiro
    • Organizer
      2019 ACR/ARP Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of IFN-γ-producing Effector B Cells in Humans: Their Relevance to the Pathogenesis of Systemic Lupus Erythematosus2019

    • Author(s)
      Kazuhiko Higashioka, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi and Hiroaki Niiro
    • Organizer
      2019 ACR/ARP Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膠原病とエフェクターB細胞2018

    • Author(s)
      新納 宏昭
    • Organizer
      第46回日本臨床免疫学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] キャッスルマン病2018

    • Author(s)
      新納 宏昭
    • Organizer
      第33回日本臨床リウマチ学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 関節リウマチにおけるIL-21産生性CD8+T細胞の役割2018

    • Author(s)
      東岡 和彦、中山 剛志、三嶋 耕司、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、有信 洋二郎、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Distinct Roles of Tfh2, SLAMF7+ Tfh1 Cells and Th1 Cells in the Pathogenesis of IgG4-RD2018

    • Author(s)
      Kazuhiko Higashioka, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi and Hiroaki Niiro.
    • Organizer
      2018 ACR/ARHP Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Deoxyribonuclease 1-like-3 Digests Self-DNA from Dead Cells and Prevents Autoimmunity2018

    • Author(s)
      (5)Shoichiro Inokuchi, Hiroki Mitoma, Shotaro Kawano, Masahiro Ayano, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi and Hiroaki Niiro
    • Organizer
      2018 ACR/ARHP Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 今日の治療指針 2019年版[デスク判]2019

    • Author(s)
      福井 次矢  (分担  新納宏昭: 高安動脈炎、巨細胞性動脈炎)
    • Total Pages
      2160
    • Publisher
      医学書院
    • ISBN
      9784260036504
    • Related Report
      2019 Research-status Report
  • [Book] 全身性エリテマトーデス診療ガイドライン20192019

    • Author(s)
      厚生労働科学研究費補助金難治性疾患等政策研究事業 自己免疫疾患に関する調査研究(自己免疫班)、日本リウマチ学会 (分担 新納宏昭)
    • Total Pages
      280
    • Publisher
      南山堂
    • ISBN
      9784525234713
    • Related Report
      2019 Research-status Report
  • [Remarks] 九州大学医学部 第一内科(病態修復内科)

    • URL

      https://www.1nai.med.kyushu-u.ac.jp

    • Related Report
      2020 Annual Research Report
  • [Remarks] 九州大学医学部 第一内科(病態修復内科)

    • URL

      http://www.1nai.med.kyushu-u.ac.jp

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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

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