Development of a novel treatment strategy based on the mechanisms that pathogenic T cells induce loss of glial connexins in CNS demyelinating disorders
| Project/Area Number |
15K19489
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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 |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Research Collaborator |
KIRA Jun-ichi
YAMASAKI Ryo
MATSUSHITA Takuya
MASAKI Katsuhisa
SUZUMURA Akio
TAKEUCHI Hideyuki
KAWANOKUCHI Jun
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 多発性硬化症 / 中枢神経脱髄疾患 / コネキシン / ギャップ結合 / Th1細胞 / インターフェロンγ / アストロサイト / ミクログリア / Cx43 / T細胞 / サイトカイン / 中枢神経脱髄性疾患 / グリア細胞 |
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| Outline of Final Research Achievements |
We previously reported early and extensive loss of astrocytic connexin 43 (Cx43) in acute demyelinating lesions of multiple sclerosis (MS) patients. Because it is widely accepted that autoimmune T cells initiate MS lesions, we hypothesized that infiltrating T cells affect Cx43 expression in astrocytes. In this research, primary mixed glial cell cultures prepared from newborn mouse brains were used. We showed that Th1 cell-conditioned medium decreased Cx43 expression in mixed glial cell cultures and interferon-γ (IFNγ) activated microglia to release interleukin (IL)-1β that reduced Cx43 gap junctions in astrocytes. Thus, Th1-dominant inflammatory states disrupt astrocytic intercellular communication and may exacerbate the inflammatory processes in demyelinating disorders. Moreover, IFNγ and Th1-prone conditions can be important targets to prevent development of extensive demyelinating lesions.
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Report
(3 results)
Research Products
(10 results)
