Establishment of treatment target for MS: Thyroid hormone receptor beta1 signaling is critically involved in the EAE pathogenesis
| Project/Area Number |
16K09704
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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 |
Neurology
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| Research Institution | Nihon University (2018)
Osaka Medical College (2016-2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宇野田 喜一 大阪医科大学, 医学部, 助教 (70751163)
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| Research Collaborator |
DOI Yoshimitsu
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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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 多発性硬化症 / 甲状腺ホルモン受容体β1 / EAE / Th17 / Treg / 自己免疫性脳炎 / 核内受容体 / 甲状腺ホルモン受容体 |
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| Outline of Final Research Achievements |
We investigated the role of thyroid hormone receptor β1 (TRβ1) in the pathogenesis of experimental allergic encephalomyelitis (EAE), utilized as animal model for MS. TRβ1 gene was highly expressed in the CNS infiltrating CD4 T cells, especially in Th17 cells, of EAE mice. TRβ1 selective agonist TRIAC exacerbated the severity of EAE, and the expression of transcriptional factor Foxp3, as a lineage specification factor of regulatory T cells, was reduced in these mice. Next, the clinical severity of EAE was significantly reduced in mice treated with THRB specific siRNA. The transcriptional levels of IL-17 in the CNS infiltrating CD4 T cells were markedly reduced, and those of Foxp3 were elevated in mice treated with THRB specific siRNA. These results suggest that TRβ1 has a key role in the mechanisms of the amelioration of EAE through the pathogenicity of Th17 cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は多発性硬化症（MS）患者の末梢血T細胞のDNAマイクロアレイの結果をもとに，核内受容体という比較的創薬の標的となりやすい分子を選んでおり，将来のMSの新規治療標的の発見と創薬という一連の成果が期待できる。また他のTh17や制御性T細胞の関与が認められる自己免疫疾患に対する汎用性のある治療成果も期待できる。近年，数多くの核内受容体が代謝性疾患だけでなく自己免疫疾患にも関与することが明らかにされているが，本研究成果は核内受容体を介した代謝性疾患と自己免疫疾患の新しいクロストークメカニズムを明らかにするという成果をもたらすことが期待される。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.2016
Author(s)
Azumagawa K, Nomura S, Shigeri Y, Jones LS, Sato DK, Nakashima I, Kashiwagi M, Tanabe T, Shimakawa S, Nakajima H, Tamai H.
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Journal Title
Brain Dev
Volume: 38
Issue: 7
Pages: 690-693
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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