Investigation of the pathogenic mechanism of Sjogren's syndrome based on intracellular metabolism and establishment of novel therapeutic strategies
| Project/Area Number |
17K19759
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Oral Science and related fields
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| Research Institution | Nihon University (2020-2022)
The University of Tokushima (2017-2019) |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | 自己免疫疾患 / シェーグレン症候群 / T細胞 / CD4陽性T細胞 / 代謝 / 細胞内代謝 |
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| Outline of Final Research Achievements |
In Sjogren's syndrome, there is a marked lymphocytic infiltrate around the lacrimal and salivary glands. Most of these lymphocytes are activated autoreactive T cells, and the exocrine function of the lacrimal and salivary glands is damaged by these activated autoreactive T cells. However, the mechanism regulating the activation of autoreactive T cells is still unknown.
Therefore, we performed a quantitative proteomic analysis of T cells isolated from lymphoid organs of both Sjogren's syndrome model mice and normal mice, and selected a molecule suggested to be associated with the pathogenesis of Sjogren's syndrome and generated a gene knockout mouse for this molecule.
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| Academic Significance and Societal Importance of the Research Achievements |
本法におけるシェーグレン症候群の患者総数は約10万人と推定されている。これまで種々の研究が行われてきたにもかかわらず、治療法は乾燥症状に対する対症療法のみで根本的治療法はまだ開発されていない。本研究では、涙腺および唾液腺を傷害する主な免疫細胞であるT細胞を対象とした定量的プロテオミクス解析を実施し、病態の増悪と相関する発現変動を示す分子を同定した。当該分子がシェーグレン症候群の有効な治療標的分子となり得る可能性は高く、臨床的波及効果は高いと考えられる。
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Report
(7 results)
Research Products
(25 results)
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[Journal Article] Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjogren Syndrome.2019
Author(s)
Otsuka K, Yamada A, Saito M, Ushio A, Sato M, Kisoda S, Shao W, Tsunematsu T, Kudo Y, Arakaki R, Ishimaru N.
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Journal Title
Am J Pathol.
Volume: 189(12)
Issue: 12
Pages: 2414-2427
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term polarization of alveolar macrophages to a profibrotic phenotype after inhalation exposure to multi-wall carbon nanotubes.2018
Author(s)
Otsuka K, Yamada K, Taquahashi Y, Arakaki R, Ushio A, Saito M, Yamada A, Tsunematsu T, Kudo Y, Kanno J, Ishimaru N.
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Journal Title
PLoS One.
Volume: 13(10)
Issue: 10
Pages: 1-18
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.2017
Author(s)
Kujiraoka S, Tsunematsu T, Sato Y, Yoshida M, Tohyama R, Tanaka M, Kobayashi Y, Kondo T, Ushio A, Otsuka K, Kurosawa M, Saito M. Yamada A, Arakaki R, Nagai H, Nikai H, Takeuchi K, Nagao T, Miyamoto Y, Ishimaru N, Kudo Y.
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Journal Title
Oral Oncol.
Volume: 69
Pages: 46-55
DOI
Related Report
Peer Reviewed / Open Access
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