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2022 Fiscal Year Research-status Report

Single-cell analysis of autoantigen-reactive B cells in systemic sclerosis and development of novel therapeutic targets

Research Project

Project/Area Number 22K16258
Research InstitutionThe University of Tokyo

Principal Investigator

深澤 毅倫  東京大学, 医学部附属病院, 特任講師 (80884056)

Project Period (FY) 2022-04-01 – 2025-03-31
Keywords全身性強皮症 / サイトカイン / B細胞 / T細胞 / モデルマウス
Outline of Annual Research Achievements

本研究では、マイクロ空間を用いた独自の技術と方法論を用い、全身性強皮症(systemic sclerosis; SSc)における自己反応性B細胞の機能と役割を明らかにすることを目的とした。まず抗Topoisomerase(topo) I抗体陽性SSc患者における末梢血中のtopoI特異的B細胞を抽出し、サイトカイン産生能などの解析を行った。様々なサイトカインのうち、Interleukin (IL)-6やIL-23などの炎症性サイトカインを産生するB細胞やIL-10やIL-35などの抑制性サイトカインを産生するB細胞がtopo I特異的B細胞集団中に存在することを見出した。今後、これらの細胞内シグナル伝達経路やサイトカインがB細胞に与える機能解析を行う予定である。
次に強皮症モデルマウス解析に関して、topoI誘発SScモデルマウスを用いた。B細胞のaffinityの上昇とサイトカイン産生能の関係について検討を行った。topo I蛋白を免疫する毎にB細胞のtopo Iに対するaffinityは強められた。low affinityなB細胞が多いモデルでは、抑制性のサイトカインを産生するB細胞の割合が多く、high affinityなB細胞が多いモデルでは、炎症性サイトカインを産生する割合が多かった。
今後は、コンディショナルノックアウトマウスを用いることで、特定のサイトカインが強皮症の病態形成に与える影響について検討を行う予定である。

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

モデルマウス作成や解析などが順調に進んでいるため。

Strategy for Future Research Activity

全身性強皮症やそのモデルマウスにおけるサイトカインの役割を明らかにし、新たな治療標的の同定に役立てることを目的とする。

  • Research Products

    (22 results)

All 2023 2022

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (8 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening2023

    • Author(s)
      Matsuda Kazuki M., Fukasawa Takemichi et al.
    • Journal Title

      Journal of Autoimmunity

      Volume: 135 Pages: 102995~102995

    • DOI

      10.1016/j.jaut.2023.102995

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term Outcomes After Rituximab Treatment for Patients With Systemic Sclerosis2023

    • Author(s)
      Kuzumi Ai、Ebata Satoshi、Fukasawa Takemichi、Matsuda Kazuki M.、Kotani Hirohito、Yoshizaki-Ogawa Asako、Sato Shinichi、Yoshizaki Ayumi
    • Journal Title

      JAMA Dermatology

      Volume: 159 Pages: 374~374

    • DOI

      10.1001/jamadermatol.2022.6340

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization2023

    • Author(s)
      Fukasawa Takemichi、Enomoto Atsushi、Yoshizaki-Ogawa Asako、Sato Shinichi、Miyagawa Kiyoshi、Yoshizaki Ayumi
    • Journal Title

      Cancers

      Volume: 15 Pages: 2054~2054

    • DOI

      10.3390/cancers15072054

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interleukin-17 pathway inhibition with brodalumab in early systemic sclerosis: analysis of a single-arm, open-label, phase 1 trial2023

    • Author(s)
      Fukasawa Takemichi、Yoshizaki Ayumi、Ebata Satoshi、Fukayama Maiko、Kuzumi Ai、Norimatsu Yuta、Matsuda Kazuki M、Kotani Hirohito、Sumida Hayakazu、Yoshizaki-Ogawa Asako、Kagebayashi Hisashi、Sato Shinichi
    • Journal Title

      Journal of the American Academy of Dermatology

      Volume: - Pages: -

    • DOI

      10.1016/j.jaad.2023.02.061

    • Peer Reviewed / Open Access
  • [Journal Article] Autoantibody Landscape Revealed by Wet Protein Array: Sum of Autoantibody Levels Reflects Disease Status2022

    • Author(s)
      Matsuda Kazuki M.、Yoshizaki Ayumi、Yamaguchi Kei、Fukuda Eriko、Okumura Taishi、Ogawa Koji、Ono Chihiro、Norimatsu Yuta、Kotani Hirohito、Hisamoto Teruyoshi、Kawanabe Ruriko、Kuzumi Ai、Fukasawa Takemichi、Ebata Satoshi、Miyagawa Takuya、Yoshizaki-Ogawa Asako、Goshima Naoki、Sato Shinichi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: -

    • DOI

      10.3389/fimmu.2022.893086

    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of rituximab in systemic sclerosis (DESIRES): open-label extension of a double-blind, investigators-initiated, randomised, placebo-controlled trial2022

    • Author(s)
      Ebata Satoshi、Yoshizaki Ayumi、Oba Koji、Kashiwabara Kosuke、Ueda Keiko、Uemura Yukari、Watadani Takeyuki、Fukasawa Takemichi、Miura Shunsuke、Yoshizaki-Ogawa Asako、Okiyama Naoko、Kodera Masanari、Hasegawa Minoru、Sato Shinichi
    • Journal Title

      The Lancet Rheumatology

      Volume: 4 Pages: e546~e555

    • DOI

      10.1016/S2665-9913(22)00131-X

    • Peer Reviewed
  • [Journal Article] Involvement of B cells in the development of systemic sclerosis2022

    • Author(s)
      Yoshizaki Ayumi、Fukasawa Takemichi、Ebata Satoshi、Yoshizaki-Ogawa Asako、Sato Shinichi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: -

    • DOI

      10.3389/fimmu.2022.938785

    • Peer Reviewed / Open Access
  • [Journal Article] Decrease in MAP3Ks expression enhances the cell death caused by hyperthermia2022

    • Author(s)
      Enomoto Atsushi、Fukasawa Takemichi、Terunuma Hiroshi、Nakagawa Keiichi、Yoshizaki Ayumi、Sato Shinichi、Miyagawa Kiyoshi
    • Journal Title

      International Journal of Hyperthermia

      Volume: 39 Pages: 200~208

    • DOI

      10.1080/02656736.2021.2024281

    • Peer Reviewed / Open Access
  • [Journal Article] Utility of nailfold capillary assessment for predicting psoriatic arthritis based on a prospective observational cohort study2022

    • Author(s)
      Fukasawa Takemichi、Toyama Satoshi、Enomoto Atsushi、Yoshizaki-Ogawa Asako、Norimatsu Yuta、Tateishi Shoko、Kanda Hiroko、Miyagawa Kiyoshi、Sato Shinichi、Yoshizaki Ayumi
    • Journal Title

      Rheumatology

      Volume: - Pages: -

    • DOI

      10.1093/rheumatology/keac664

    • Peer Reviewed
  • [Journal Article] Predictors of rituximab effect on modified Rodnan skin score in systemic sclerosis: a machine-learning analysis of the DesiReS trial2022

    • Author(s)
      Ebata Satoshi、Oba Koji、Kashiwabara Kosuke、Ueda Keiko、Uemura Yukari、Watadani Takeyuki、Fukasawa Takemichi、Miura Shunsuke、Yoshizaki-Ogawa Asako、Yoshihide Asano、Yoshizaki Ayumi、Sato Shinichi
    • Journal Title

      Rheumatology

      Volume: 61 Pages: 4364~4373

    • DOI

      10.1093/rheumatology/keac023

    • Peer Reviewed
  • [Journal Article] Involvement of Molecular Mechanisms between T/B Cells and IL-23: From Palmoplantar Pustulosis to Autoimmune Diseases2022

    • Author(s)
      Fukasawa Takemichi、Yoshizaki-Ogawa Asako、Enomoto Atsushi、Miyagawa Kiyoshi、Sato Shinichi、Yoshizaki Ayumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 8261~8261

    • DOI

      10.3390/ijms23158261

    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacotherapy of Itch-Antihistamines and Histamine Receptors as G Protein-Coupled Receptors2022

    • Author(s)
      Fukasawa Takemichi、Yoshizaki-Ogawa Asako、Enomoto Atsushi、Miyagawa Kiyoshi、Sato Shinichi、Yoshizaki Ayumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 6579~6579

    • DOI

      10.3390/ijms23126579

    • Peer Reviewed / Open Access
  • [Journal Article] Serum C-X-C Chemokine Ligand 1 Levels in Patients with Systemic Sclerosis: Relationship of Clinical and Laboratory Observations to Anti-CD20 Monoclonal Antibody Administration2022

    • Author(s)
      Kawanabe Ruriko、Yoshizaki Ayumi、Matsuda Kazuki M.、Kotani Hirohito、Hisamoto Teruyoshi、Norimatsu Yuta、Kuzumi Ai、Fukasawa Takemichi、Ebata Satoshi、Yoshizaki-Ogawa Asako、Sato Shinichi
    • Journal Title

      Life

      Volume: 12 Pages: 646~646

    • DOI

      10.3390/life12050646

    • Peer Reviewed / Open Access
  • [Journal Article] 強皮症に伴う間質性肺炎の胸部CT画像を対象とした診断補助システム2022

    • Author(s)
      吉田 純司、朱 奕綸、吉崎 歩、深澤 毅倫、阿部 雅人
    • Journal Title

      AI・データサイエンス論文集

      Volume: 3 Pages: 346~352

    • DOI

      10.11532/jsceiii.3.J2_346

    • Peer Reviewed / Open Access
  • [Presentation] PHARMACOKINETICS, SAFETY, AND EFFICACY OF SUBCUTANEOUS BRODALUMAB FOR SYSTEMIC SCLEROSIS WITH MODERATE-TO-SEVERE SKIN THICKENING: A SINGLE-ARM, OPEN-LABEL, MULTI-DOSE, PHASE 1 TRIAL.2022

    • Author(s)
      T Fukasawa, et al.
    • Organizer
      EULAR
    • Int'l Joint Research
  • [Presentation] EFFICACY AND SAFETY OF SUBCUTANEOUS BRODALUMAB, A FULLY HUMAN ANTI-IL-17RA MONOCLONAL ANTIBODY, FOR SYSTEMIC SCLEROSIS WITH MODERATE-TO-SEVERE SKIN THICKENING: A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND PHASE 3 STUDY.2022

    • Author(s)
      T Fukasawa, et al.
    • Organizer
      EULAR
    • Int'l Joint Research
  • [Presentation] Single cell level protein analysis of autoantigen-reactive B cells in systemic sclerosis and the murine model.2022

    • Author(s)
      T Fukasawa, et al.
    • Organizer
      ESDR
    • Int'l Joint Research
  • [Presentation] 様々な細胞や疾患におけるIL-17とIL-17受容体の役割2022

    • Author(s)
      深澤 毅倫、吉崎 歩、佐藤 伸一
    • Organizer
      第50回日本臨床免疫学会総会
  • [Presentation] 全身性強皮症およびモデルマウスにおける自己抗原反応性B細胞の単一細胞解析2022

    • Author(s)
      深澤 毅倫、吉崎 歩、佐藤 伸一
    • Organizer
      第50回日本臨床免疫学会総会
  • [Presentation] 様々な細胞や疾患におけるIL-17とIL-17受容体の役割2022

    • Author(s)
      深澤 毅倫、吉崎 歩、佐藤 伸一
    • Organizer
      第73回日本皮膚科学会中部支部学術大会
  • [Presentation] Role of IL-17 and IL-17 receptors in various cells and diseases2022

    • Author(s)
      Takemichi Fukasawa, Ayumi Yoshizaki, Shinichi Sato
    • Organizer
      47th JSID
    • Int'l Joint Research
  • [Presentation] Single cell protein analysis of autoantigen-reactive B cells in the autoimmune disease and the murine model2022

    • Author(s)
      Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki, Shinichi Sato, and Ayumi Yoshizaki
    • Organizer
      47th JSID
    • Int'l Joint Research

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Published: 2023-12-25  

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