Role of cytokine-producing effector B cells in autoimmune diseases

• Project/Area Number: 18K08410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kyushu 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: ¥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。

Research Products

• [Journal Article] Type 1 helper T cells generate CXCL9/10-producing T-bet + effector B cells potentially involved in the pathogenesis of rheumatoid arthritis (2021)
  • 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
  • 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
  • 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 sclerosis (2020)
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines (2019)
  • 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
  • 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
  • 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 study (2018)
  • 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
  • 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
  • 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
• [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
• [Presentation] A novel IL-21-producing CD8+ T cell subset involved in the pathogenesis of rheumatoid arthritis (2019)
  • Author(s): Kazuhiko Higashioka, Hiroaki Niiro
  • Organizer: Keystone Symposia B Cell-T Cell Interactions
  • Int'l Joint Research
• [Presentation] Activation of caspase-1 in CD16-positive monocyte and correlation with disease activity in systemeic lupus erythmatosus (2019)
  • 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
• [Presentation] Pathologic role of activated SLAMF7+Tfh1 cells in facilitating IgG4 production by B cells in IgG4-related disease (2019)
  • 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
• [Presentation] Tumor Necrosis Factor Receptor 2 Signaling Potentiates Proliferation and Suppressive Activities of Follicular Regulatory T Cells (2019)
  • 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
  • Int'l Joint Research
• [Presentation] Identification of IFN-γ-producing Effector B Cells in Humans: Their Relevance to the Pathogenesis of Systemic Lupus Erythematosus (2019)
  • 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
  • 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
  • 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
  • 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
• [Presentation] Distinct Roles of Tfh2, SLAMF7+ Tfh1 Cells and Th1 Cells in the Pathogenesis of IgG4-RD (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Deoxyribonuclease 1-like-3 Digests Self-DNA from Dead Cells and Prevents Autoimmunity (2018)
  • 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
  • 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
• [Book] 全身性エリテマトーデス診療ガイドライン2019 (2019)
  • 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
• [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
• [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