Analysis of the effect of cytokine production by autoantigen-reactive B cells in systemic sclerosis on other immune systems.
Project/Area Number |
20K22925
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0903:Organ-based internal medicine and related fields
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 自己反応性B細胞 / サイトカイン / 全身性強皮症 / T細胞 / microfluidics / 単一細胞解析 / B細胞 / affinity / 医工連携 |
Outline of Research at the Start |
全身性強皮症は全身性自己免疫疾患で、本邦における指定難病であり、有効な治療法はない。近年、この病態形成には免疫系の主要構成因子であるB細胞、中でも自己抗体産生の担い手である自己抗原反応性B細胞が全身性強皮症の病態に重要な役割を果たすことが想定されるが、数は少なく、直接的な病原性の解析法が十分に確立していない。今回の研究では、医工連携研究によって開発された少数細胞のタンパク質レベルでの解析システムを用い、全身性強皮症における自己抗原反応性B細胞の役割を検討し、広く自己免疫疾患における自己抗原反応性B細胞の役割の理解を深め、新たな治療ターゲットの同定と治療法開発へとつなげることを目指す。
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Outline of Final Research Achievements |
In this study, we used original microspace-based techniques and methodologies to elucidate the function and role of autoreactive B cells in systemic sclerosis (SSc). Regarding the relationship between affinity to topoI antigen and cytokine production capacity, the proportion of B cells producing inflammatory cytokines such as IL-6 and IL-23 was higher in high affinity B cells, and the amount produced was also higher. Similarly, low affinity B cells produced a higher percentage of B cells that produced IL-10 and IL-35 inhibitory cytokines, and the amount produced was also higher. The former was also shown to induce Th17 cells and the latter Treg cells.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、自己抗原反応性B細胞の機能を明らかとすることで、数あるB細胞集団中から、病原性を有するB細胞集団を明らかとする。さらに我々の技術では、少数の自己抗原反応性B細胞のタンパク分析を可能としており、表面抗原の分析によって新たな治療ターゲットの同定につながることが期待される。このような研究は他に類が無く、他の自己免疫疾患においても応用可能であることから、革新的かつ創造的な研究となることが期待される。
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Clinical Significance of Anti-U1 Ribonucleoprotein Antibody in Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis Patients: A Retrospective Observational Study2021
Author(s)
Kazuki M Matsuda, Ayumi Yoshizaki, Hirohito Kotani, Ai Kuzumi, Maiko Fukayama, Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Koji Oba, Shinichi Sato
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Journal Title
Archives of Clinical and Biomedical Research
Volume: 5
Pages: 76-84
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cutaneous Sarcoidosis as a Predictor of Cardiac Sarcoidosis2021
Author(s)
Yuta Norimatsu, Ayumi Yoshizaki, Yuki Ohno, Yuka Mizuno, Haruka Watanabe, Hirohito Kotani, Kazuki M Matsuda, Maiko Fukayama, Ai Kuzumi, Satoshi Ebata, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Shinichi Sato
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Journal Title
Archives of Clinical and Biomedical Research
Volume: 5
Pages: 368-375
Related Report
Peer Reviewed / Open Access
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[Journal Article] Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model.2021
Author(s)
Fukasawa T, Yoshizaki A, Ebata S, Yoshizaki-Ogawa A, Asano Y, Enomoto A, Miyagawa K, Kazoe Y, Mawatari K, Kitamori T, Sato S.
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Journal Title
Elife
Volume: 10
Pages: 5-5
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial.2021
Author(s)
Ebata, S., Yoshizaki, A., Oba, K., Kashiwabara, K., Ueda, K., Uemura, Y., Watadani, T., Fukasawa, T., Miura, S., Yoshizaki-Ogawa, A., Asano, Y., Okiyama, N., Kodera, M., Hasegawa, M., & Sato, S.
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Journal Title
Lancet Rheumatology
Volume: 3
Pages: 489-497
Related Report
Peer Reviewed
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[Presentation] Safety and Efficacy of Rituximab for Systemic Sclerosis: A Double-Blind, Parallel-Group Comparison, Investigators Initiated Confirmatory Randomized Clinical Trial (DESIRES Study)2021
Author(s)
Satoshi Ebata, Ayumi Yoshizaki, Koji Oba, Kosuke Kashiwabara, Keiko Ueda, Yukari Umemura, Takeyuki Watadani, Takemichi Fukasawa, Shunsuke Miura, Asako Yoshizaki-Ogawa, Yoshihide Asano, Naoko Okiyama, Masanari Kodera, Minoru Hasegawa and Shinichi Sato
Organizer
American college of rheumatology 2021
Related Report
Int'l Joint Research
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