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Functional analysis of antigen-specific B cells in systemic sclerosis using micro space

Research Project

Project/Area Number 17K16324
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionThe University of Tokyo

Principal Investigator

Yoshizaki Ayumi  東京大学, 医学部附属病院, 講師 (40530415)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords強皮症 / 自己免疫疾患 / B細胞 / サイトカイン / マイクロ・ナノデバイス
Outline of Final Research Achievements

Recent advances in immunology have suggested that B cells play a central role in the immune system. B cells are also important in autoimmune diseases, and in particular, self-antigen stimulation via B cell receptors induces activation of autoreactive B cells and cytokine production, resulting in significant involvement in the development and progression of diseases. However, only a few autoreactive B cells exist in the patients, and direct examination of its function such as reactivity to self antigens, cytokine production, and interaction with other cells is technically difficult. Therefore, there are no studies which analyze the role of autoreactive B cells directly. In this study, we examined the function of autoreactive B cells in systemic sclerosis using proprietary techniques and methodologies using microspace.

Academic Significance and Societal Importance of the Research Achievements

本研究では新しい測定法を用い、SSc患者より得られた自己反応性B細胞の機能解析を行った。具体的にはガラスマイクロチップ上に作成されたマイクロ空間を用い、topo I抗原特異的B細胞から産生されるサイトカインの測定を行い、モデルマウスへの養子移入を介して自己反応性B細胞の持つ機能を検討した。本研究により、自己反応性B細胞が産生するサイトカインは、自己抗原に対する抗原親和性によって変化することが明らかとなった。これまでブラックボックスであった自己抗原反応性B細胞の機能を直接的に検討したはじめての研究であり、今後の強皮症病態解明に寄与すると考えられる。

Report

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

    (18 results)

All 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 7 results,  Invited: 4 results)

  • [Journal Article] Serum levels of human β-defensin 2: possible association with fibrosis and vasculopathy in patients with systemic sclerosis.2019

    • Author(s)
      Kuzumi A, Yoshizaki A, Fukasawa T, Ebata S, Miura S, Yoshizaki A, Sumida H, Asano Y, Sato S.
    • Journal Title

      J Eur Acad Dermatol Venereol.

      Volume: In press Issue: 7

    • DOI

      10.1111/jdv.15546

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-10-Producing Regulatory B Cells Are Decreased in Patients with Atopic Dermatitis.2019

    • Author(s)
      Yoshihara Y, Ishiuji Y, Yoshizaki A, Kurita M, Hayashi M, Ishiji T, Nakagawa H, Asahina A, Yanaba K.
    • Journal Title

      J Invest Dermatol.

      Volume: 139 Issue: 2 Pages: 475-478

    • DOI

      10.1016/j.jid.2018.08.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An orally-active adiponectin receptor agonist mitigates cutaneous fibrosis, inflammation and microvascular pathology in a murine model of systemic sclerosis2018

    • Author(s)
      Yamashita Takashi、Lakota Katja、Taniguchi Takashi、Yoshizaki Ayumi、Sato Shinichi、Hong Wen、Zhou Xingchun、Sodin-Semrl Snezn、Fang Feng、Asano Yoshihide、Varga John
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 11843-11843

    • DOI

      10.1038/s41598-018-29901-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease.2018

    • Author(s)
      Numajiri H, Yoshizaki A, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Sumida H, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S.
    • Journal Title

      J Dermatol.

      Volume: 45 Issue: 10 Pages: 1221-1224

    • DOI

      10.1111/1346-8138.14580

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serum interleukin-34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease.2018

    • Author(s)
      Kuzumi A, Yoshizaki A, Toyama S, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Asano Y, Sato S.
    • Journal Title

      J Dermatol.

      Volume: 28 Issue: 10 Pages: 314-319

    • DOI

      10.1111/1346-8138.14538

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis2017

    • Author(s)
      sclerosis. Taniguchi T, Miyagawa T, Tamaki Z, Nakamura K, Yamashita T, Saigusa R, Takahashi T, Toyama T, Ichimura Y, Yoshizaki A, Tada Y, Sugaya M, Kadono T, Sato S, Asano Y.
    • Journal Title

      Arch Dermatol Res.

      Volume: 309 Issue: 10 Pages: 833

    • DOI

      10.1007/s00403-017-1786-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A potential contribution of psoriasin to vascular and epithelial abnormalities and inflammation in systemic sclerosis2017

    • Author(s)
      Takahashi T.、Asano Y.、Yamashita T.、Nakamura K.、Saigusa R.、Miura S.、Ichimura Y.、Toyama T.、Hirabayashi M.、Taniguchi T.、Yoshizaki A.、Sato S.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 32 Issue: 2 Pages: 291-297

    • DOI

      10.1111/jdv.14459

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis2017

    • Author(s)
      Fukasawa Takemichi、Yoshizaki Ayumi、Ebata Satoshi、Nakamura Kouki、Saigusa Ryosuke、Miura Syunsuke、Yamashita Takashi、Hirabayashi Megumi、Ichimura Yohei、Taniguchi Takashi、Asano Yoshihide、Shimizu Hisashi、Kazoe Yutaka、Mawatari Kazuma、Kitamori Takehiko、Sato Shinichi
    • Journal Title

      Arthritis & Rheumatology

      Volume: 69 Issue: 9 Pages: 1879-1890

    • DOI

      10.1002/art.40164

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic Sclerosis.2017

    • Author(s)
      Taniguchi T, Asano Y, Nakamura K, Yamashita T, Saigusa R, Ichimura Y, Takahashi T, Toyama T, Yoshizaki A, Sato S.
    • Journal Title

      J Rheumatol.

      Volume: 44 Issue: 8 Pages: 1198-1205

    • DOI

      10.3899/jrheum.161092

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma.2017

    • Author(s)
      Takehiro Takahashi, Yoshihide Asano, Koji Sugawara, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Kaname Akamata, Shinji Noda, Ayumi Yoshizaki, Daisuke Tsuruta, Maria Trojanowska, and Shinichi Sato
    • Journal Title

      Journal of Experimental Medicine

      Volume: 214 Issue: 4 Pages: 1129-1151

    • DOI

      10.1084/jem.20160247

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Direct Interaction between Autoreactive B Cells and Endothelial Colony Forming Cells Induces Cytokine Production from B cells through B Cell Receptor and IL-6-JAK2-STAT3 Signaling Pathway, Suppressing Proliferation of Endothelial Colony Forming Cells in Systemic Scleosis2018

    • Author(s)
      Fukasawa T, Yoshizaki A, Ebata S, Nakamura K, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S
    • Organizer
      2018 ACR (82th)/ARHP (53th) Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elevated Serum Interleukin-34 Levels Are Correlated with Interstitial Lung isease in Systemic Sclerosis2018

    • Author(s)
      Suga H, Kuzumi A, Asano Y, Yoshizaki A, Sato S
    • Organizer
      2018 ACR (82th)/ARHP (53th) Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 医工連携研究による単一細胞サイトカイン解析が紐解く、自己抗原特異的B細胞の全身性強皮症における役割2018

    • Author(s)
      吉崎 歩
    • Organizer
      第46回日本臨床免疫学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Single cell analysis revealed that autoantigen-reactive B cells contribute to the development of systemic sclerosis2018

    • Author(s)
      Ayumi Yoshizaki
    • Organizer
      11th Asian Dermatological Congress held in conjunction with the 18th Dubai World Dermatology & Laser Conference and Exhibition-Dubai Derma
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The cytokine profile revealed with the high sensitive microfluidic-ELISA system associates with the efficacy of antibody drugs in psoriasis2018

    • Author(s)
      Fukasawa T, Yoshizaki A, Ebata S, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S
    • Organizer
      11th Asian Dermatological Congress held in conjunction with the 18th Dubai World Dermatology & Laser Conference and Exhibition-Dubai Derma
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cytokine profile revealed by medical-engineering collaboration study associates with the efficacy of antibody drugs in psoriasis2017

    • Author(s)
      Ayumi Yoshizaki
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Medical-engineering collaboration brings novel strategies for revealing the pathogenesis of autoimmune diseases2017

    • Author(s)
      Ayumi Yoshizaki
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Single cell analysis revealed that the response to cyclophosphamide therapy is regulated by B cells in systemic sclerosis-associated interstitial lung disease2017

    • Author(s)
      Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Takasgi Yamashita, Shunsuke Miura, Ryosuke Saigusa, Megumi Hirabayashi, Asako Yoshizaki, Kaname Akamata, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato
    • Organizer
      2017 ACR (81th)/ARHP (52th) Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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