Molecular Mechanism of Autoimmune Germinal Center Reaction and a New Therapeutic Strategy for Autoimmunity
| Project/Area Number |
18K19648
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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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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIMARU Naozumi 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (60314879)
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| Co-Investigator(Kenkyū-buntansha) |
新垣 理恵子 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (00193061)
工藤 保誠 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (50314753)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 自己免疫疾患 / 自己抗体 / Tfh細胞 / GC反応 / シェーグレン症候群 / 自己免疫性胚中心反応 / Ascl2 / 疾患モデル / GCB細胞 / 胚中心反応 |
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| Outline of Final Research Achievements |
Follicular helper T (Tfh) cells are known to contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Here, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren’s syndrome (SS) wherein the mice underwent neonatal thymectomy (Tx). The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were upregulated in peripheral CD25－ CD4+ T cells in SS model mice compared to those in control mice. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity.
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫疾患は自身の臓器や細胞が免疫反応の標的となる疾患であり、自己と非自己を厳密に区別するはずの免疫システムの適切な機能から明らかに逸脱している。全身どの臓器も標的となり、単一の原因ではなく多因子による発症機序が存在しているため、病態メカニズムは複雑で、自己免疫疾患の診断は困難な場合があり、病因論に基づいた根本的な治療法の開発には至っていないのが現状である。本研究では、自己免疫性胚中心反応という新たな概念を提唱するとともに、その詳細な機構を明らかにし、病態と自己抗体の新たな関係を解明した点で、重要な内容を含む研究であり、今後、臨床応用への可能性が十分示された。
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Report
(3 results)
Research Products
(51 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] Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1.2019
Author(s)
Miyazaki A, Sugimoto A, Yoshizaki K, Kawarabayashi K, Iwata K, Kurogoushi R, Kitamura T, Otsuka K, Hasegawa T, Akazawa Y, Fukumoto S, Ishimaru N, Iwamoto T.
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Journal Title
Sci Rep.
Volume: 9(1)
Issue: 1
Pages: 14762-14762
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification.2019
Author(s)
Nakatomi C, Nakatomi M, Matsubara T, Komori T, Doi-Inoue T, Ishimaru N, Weih F, Iwamoto T, Matsuda M, Kokabu S, Jimi E.
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Journal Title
Bone
Volume: 121
Issue: 3
Pages: 29-41
DOI
Related Report
Peer Reviewed
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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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[Presentation] NF-κB2 Controls the Migratory Activity of Memory T Cells to the Target Tissues in a Mouse Model of Sjogren’s Syndrome by Regulating Expression of CXCR4.2018
Author(s)
Rieko Arakaki, Mie Kurosawa,,Akiko Yamada, Aya Ushio, Satoko Kujiraoka, Kunihiro Otsuka, Takaaki Tsunematsu, Yasusei Kudo, Jonathan Sprent, and Naozumi Ishimaru
Organizer
11th International Congress on Autoimmunity
Related Report
Int'l Joint Research
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