A molecular basis of inflammatory Th17 cells in autoimmune diseases
Project/Area Number |
16H06233
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Immunology
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Research Institution | Kyoto University |
Principal Investigator |
Hirota Keiji 京都大学, ウイルス・再生医科学研究所, 准教授 (90631250)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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Keywords | Th17細胞 / 自己免疫疾患モデル / Th17 / GM-CSF / 自己免疫性関節炎 / IL-17 |
Outline of Final Research Achievements |
In this study, we investigated an inflammatory cascade mediated by autoimmune Th17 cells and analyzed inflammatory networks starting from Th17 cells and their constituent factors. In particular, we elucidated the significance and regulatory mechanism of GM-CSF-producing inflammatory subsets in autoimmune arthritis, and identified synovial innate lymphoid cells that highly produced GM-CSF, a novel arthritogenic inflammatory subset. We also identified Satb1 as a molecule involved in the regulation of an effector gene expression network in autoimmune Th17 cells. These results advanced our understanding of how chronic inflammation is maintained by the interaction between immune cells and mesenchymal cells.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、炎症性Th17細胞を起点とした炎症局所における細胞間相互作用とその制御因子を明らかにした。今後、これらの成果を標的とした次世代の予防法・治療法開発にも研究展開が可能である。GM-CSF阻害剤を用いた治験では関節リウマチに対する高い有効性が報告されており、今後、GM-CSFを産生する自然リンパ球を標的とした治療薬開発も期待できる。また、Satb1を標的とした炎症性Th17細胞の制御法の確立は、Th17細胞が起こす自己免疫疾患に対する免疫学的な新規治療法になりうる可能性がある。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.2017
Author(s)
Kitagawa Y, Ohkura N, Kidani Y, Vandenbon A, Hirota K, Kawakami R, Yasuda K, Motooka D, Nakamura S, Kondo M, Taniuchi I, Kohwi-Shigematsu T, Sakaguchi S.
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Journal Title
Nat Immunol.
Volume: 18(2)
Issue: 2
Pages: 173-183
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine.2016
Author(s)
Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, and Takeda K
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Journal Title
Arthritis Rheum
Volume: 68
Issue: 11
Pages: 2646-2661
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Inflammatory cascade of autoimmune arthritis by Th17 cells and GM-CSF-producing ILCs2019
Author(s)
Hirota K, Hashimoto M, Ito Y, Matsuura M, Ito H, Tanaka M, Watanabe H, Kondoh G, Tanaka A, Yasuda K, Kopf M, Potocnik AJ, Stockinger B, Sakaguchi N, Sakaguchi S
Organizer
Keystone symposium
Related Report
Int'l Joint Research
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[Presentation] An inflammatory cellular cascade of autoimmune Th17 cells, GM-CSF-producing synovial ILCs and stromal cells in the development of autoimmune arthritis2018
Author(s)
Hirota K, Hashimoto M, Ito Y, Matsuura M, Ito H, Tanaka M, Watanabe H, Kondoh G, Tanaka A, Yasuda K, Kopf M, Potocnik AJ, Stockinger B, Sakaguchi N, Sakaguchi S
Organizer
Kyoto T cell Conference
Related Report
Int'l Joint Research
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[Presentation] GM-CSF-producing synovial ILCs exacerbate Th17-mediated autoimmune arthritis2018
Author(s)
Hirota K, Hashimoto M, Ito Y, Matsuura M, Ito H, Tanaka M, Watanabe H, Kondoh G, Tanaka A, Yasuda K, Kopf M, Potocnik AJ, Stockinger B, Sakaguchi N, Sakaguchi S
Organizer
The 3rd International Conference on Innate Lymphoid Cells
Related Report
Int'l Joint Research
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