Understanding the mechanisms of IRF5-selective regulation towards the development of novel SLE treatment
| Project/Area Number |
16K19161
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Yokohama City University |
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Principal Investigator |
Ban Tatsuma 横浜市立大学, 医学部, 助教 (50635357)
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| Research Collaborator |
TAMURA Tomohiko
NISHIYAMA Akira
SATO Go
KIKUCHI Masako
MANABE Akio
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 転写因子 / IRF5 / 自然免疫応答 / 全身性エリテマトーデス / MAPキナーゼ / 自己免疫疾患 / 全身性エリテマトーデス (SLE) / 免疫学 |
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| Outline of Final Research Achievements |
In this study, aiming to identify novel therapeutic targets for systemic lupus erythematosus (SLE), a refractory autoimmune disease, we analyzed the selective regulatory mechanism of the transcription factor IRF5, which is involved in the pathogenesis of SLE. As a result, it was suggested that transcription factors activated via the MAP kinase (MAPK) pathway are involved in selective control of IRF5 activity. Furthermore, inhibition of MAPK resulted in suppression of IRF5-dependent innate immune responses in mice. Clarifying the mechanism of IRF5 regulation by transcription factors activated via the MAPK pathway might lead to the development of therapy for SLE and other IRF5-related diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで不明であったMAPキナーゼ経路による選択的なIRF5活性制御機構が存在することを明らかにした。IRF5はSLEのみならず、シェーグレン症候群や全身性強皮症など他の自己免疫疾患の病態発症とも関連するため、IRF5選択的制御機構の解明はこれらの疾患の治療法開発にも繋がると期待できる。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.2016
Author(s)
Ban T., Sato G.R., Nishiyama A., Akiyama A., Takasuna M., Umehara M., Suzuki S., Ichino M., Matsunaga S., Kimura A., Kimura Y., Yanai H., Miyashita S., Kuromitsu J., Tsukahara K., Yoshimatsu K., Endo I., Yamamoto T., Hirano H., Ryo A., Taniguchi T., Tamura T.
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Journal Title
Immunity
Volume: 45
Issue: 2
Pages: 319-332
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Selective suppression of IRF5 activity by Lyn in the TLR-MyD88 pathway restrains the development of SLE-like disease2017
Author(s)
Ban T, Sato GR, Nishiyama A, Matsunaga S, Kimura A, Kimura Y, Yanai H, Matsumoto Y, Hihara H, Yamamoto T, Hirano H, Ryo A, Tsukahara K, Yoshimatsu K, Taniguchi T, Tamura T
Organizer
Cytokines 2017 (5th Annual Meeting of the International Cytokine & Interferon Society)
Related Report
Int'l Joint Research
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[Presentation] A critical link between Lyn-mediated suppression of the TLR-MyD88-IRF5 pathway and the development of SLE-like disease2016
Author(s)
Ban T, Sato GR, Nishiyama A, Akiyama A, Takasuna M, Umehara M, Suzuki S, Ichino M, Matsunaga S, Kimura A, Kimura Y, Yanai H, Miyashita S, Kuromitsu J, Tsukahara K, Yoshimatsu K, Endo I, Yamamoto T, Hirano H, Ryo A, Taniguchi T, Tamura T
Organizer
The Annual Meeting of the American Association of Immunologists 2016
Place of Presentation
Seattle (USA)
Year and Date
2016-05-13
Related Report
Int'l Joint Research
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