Establishment of regulation for autoimmune diseases targeting new T cell subsets
| Project/Area Number |
18H02636
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Komatsu Noriko 東京大学, 大学院医学系研究科(医学部), 助教 (20553358)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 自己免疫疾患 / 関節リウマチ / j自己免疫疾患 / T細胞 |
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| Outline of Final Research Achievements |
In autoimmune diseases such as rheumatoid arthritis, it is urgently necessary to establish novel fundamental therapies based on understanding the mechanism. In this study, we aimed to clarify the molecular mechanisms that govern the pathogenic T cells we identified previously as well as synovial fibroblasts which interact with the pathogenic T cells. By genetic analysis, we proved that synovial fibroblasts are primary cells that induce bone erosion in arthritis in vivo, suggesting the importance of the pathogenic T -synovial fibroblast axis in arthritis. We further clarified a part of the molecular mechanisms that explain pathogenic T cells and synovial fibroblasts. This study will contribute to the establishment of novel therapies for autoimmune diseases including rheumatoid arthritis.
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫疾患のメカニズムはいまだ不明な点が多く根本的な治療法が存在しない。本研究では代表的な自己免疫疾患である関節リウマチにおいて、病原性を発揮するT細胞と、炎症関節部位に特異的に存在し病原性T細胞と相互作用をする間葉系細胞に着眼し、両者の病原性をつかさどる分子基盤の一端を明らかにした。さらに本研究で樹立した研究基盤を活用し、関節リウマチの骨破壊の一形態である傍関節性骨粗鬆症の機構の解明に繋げた。したがって本研究成果は関節リウマチをはじめとする自己免疫疾患の病態理解と治療法の開発に貢献する知見を提供するものとして意義があると考えられる。
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Report
(5 results)
Research Products
(34 results)
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[Journal Article] tepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution.2021
Author(s)
Tsukasaki M, Huynh NC, Okamoto K, Muro R, Terashima A, Kurikawa Y, Komatsu N, Pluemsakunthai W, Nitta T, Abe T, Kiyonari H, Okamura T, Sakai M, Matsukawa T, Matsumoto M, Kobayashi Y, Penninger JM, Takayanagi H
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Journal Title
Nat Metab
Volume: 2
Issue: 12
Pages: 1382-1390
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells2020
Author(s)
Daisuke Takahashi, Naomi Hoshina, Yuma Kabumoto, Yuichi Maeda, Akari Suzuki, Hiyori Tanabe, Junya Isobe, Takahiro Yamada, Kisara Muroi, Yuto Yanagisawa, Atsuo Nakamura, ... Koji Hase
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Journal Title
EBioMedicine
Volume: 58
Pages: 102913-102913
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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