Exploration of therapeutic targets which are involved in the pathogenesis of Sjogren's syndrome aiming at ion channels.
| Project/Area Number |
16K09905
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Keio University |
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Principal Investigator |
Yoshimoto Keiko 慶應義塾大学, 医学部(信濃町), 研究員 (20383292)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | シェーグレン症候群 / BAFF / BAFF受容体 / イオンチャンネル / シェーグレン症候群ｎ / 単球 / B細胞 / 自己抗体 / IL-6 / IgG / 膠原病学 |
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| Outline of Final Research Achievements |
BAFF and its receptor (BR3) are involved in the pathogenesis of Sjogren’s syndrome (SS). We demonstrated that the expression levels of BR3 and a voltage-gated sodium channel in SS monocytes were significantly higher than those of healthy controls and that elevation was correlated with serum IgG level of the patients. In addition, we have successfully discovered a low molecular weight compound which has inhibitory activities against both BAFF signaling pathways and a sodium channel. In this study, we tested the effects of this compound on production of autoantibodies and inflammatory cytokines by using autoimmune model mice. As a results, we found that this compound inhibited production of anti-dsDNA antibody and inflammatory cytokines, such as IL-6 and IL-10. Moreover, this compound also suppressed infiltration of B cells into the organs, such as lachrymal glands and kidney. Notably, we have found a novel compound which is expected more efficacy on the suppression of B cell function.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は免疫難病であるシェーグレン症候群（SS）の患者単球の異常活性化機構と病態への関与を明らかにするものである。具体的には患者末梢血単球で発現が亢進しているイオンチャンネル同定し、これを介したシグナルとBAFFシグナルの関与を明らかにした。さらに研究代表者らはこの機構を阻害する作用を有する独自の化合物を得て、SSモデル動物での薬効薬理試験を実施し、有効性を検証することに成功した。本研究はSSの発症メカニズムを明らかにするという点で学術的に有意義であるばかりでなく、きわめて独創性の高い治療標的を見出すことにつながり、SSの新規な治療法の開発という点においても有用である。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.2018
Author(s)
Tasaki S, Suzuki K, Kassai Y, Takeshita M, Murota A, Kondo Y, Ando T, Nakayama Y, Okuzono Y, Takiguchi M, Kurisu R, Miyazaki T, Yoshimoto K, Yasuoka H, Yamaoka K, Morita R, Yoshimura A, Toyoshiba H, Takeuchi T.
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Journal Title
Nat Commun
Volume: 9(1)
Issue: 1
Pages: 2755-2755
DOI
Related Report
Peer Reviewed
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[Journal Article] Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.2017
Author(s)
Tasaki S1,2, Suzuki K3, Nishikawa A3, Kassai Y4, Takiguchi M4, Kurisu R4, Okuzono Y4, Miyazaki T4,5, Takeshita M3, Yoshimoto K3, Yasuoka H3, Yamaoka K3, Ikeura K6, Tsunoda K6, Morita R7, Yoshimura A7, Toyoshiba H1, Takeuchi T3.
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Journal Title
Ann Rheum Dis
Volume: 76
Issue: 8
Pages: 1458-1466
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of definitive serum biomarkers associated with disease activity in primary Sjogren's syndrome.2016
Author(s)
Nishikawa A, Suzuki K, Kassai Y, Gotou Y, Takiguchi M, Miyazaki T, Yoshimoto K, Yasuoka H, Yamaoka K, Morita R, Yoshimura A, Takeuchi T.
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Journal Title
Arthritis Res Ther.
Volume: 18
Issue: 1
Pages: 106-106
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Low molecular weight compounds which inhibit BAFF binding to its receptor, BR3, suppress activation of monocytes.2016
Author(s)
Yoshimoto K, Ishioka E, Nishikawa A, Suzuki K, Ito T, Sugano T, Yamada H, Okuda A, Okuda H, Ishikawa H, Doi T, Hirokawa T, Takeuchi T
Organizer
IMMUNOLOGY 2016
Place of Presentation
Seattle Convention Center シアトル（アメリカ）
Year and Date
2016-05-13
Related Report
Int'l Joint Research
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