2019 Fiscal Year Final Research Report
The role of exosome-derived from human T-cell leukemia virus type 1 (HTLV-1) infected cells in the pathogenesis of HTLV-1-positive rheumatoid arthritis.
| Project/Area Number |
17K09979
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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 | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岡山 昭彦 宮崎大学, 医学部, 教授 (70204047)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | エクソソーム / ヒトT細胞白血病ウイルス / 関節リウマチ |
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| Outline of Final Research Achievements |
The aim of this study is to investigate the role of exosomes-derived from HTLV-1 infected cells in the inflammatory responses of rheumatoid arthritis synovial fibroblasts (RASFs). The expression of cytokines mRNA in RASFs was increased by exosomes and inflammatory cytokines such as IFNγ and TNFα. The silencing of both RIG-I and its cooperative binding protein using siRNA decreased the expression of cytokines mRNA in RASFs which were stimulated by exosomes and IFNγ. These results suggested that exosomes-derived from HTLV-1 infected cells may act as inflammatory mediator against RASFs. Both RIG-I and its cooperative binding protein may play important role in the exosome-induced signal pathway in RASFs.
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| Free Research Field |
膠原病リウマチ学
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| Academic Significance and Societal Importance of the Research Achievements |
HTLV-1陽性関節リウマチは炎症反応が高く，TNF阻害療法など既存の抗リウマチ治療に治療抵抗性を示すことが報告されている．その詳細な炎症病態は不明な点が多い．本研究では，HTLV-1感染細胞由来エクソソームが炎症性メディエータとして関節リウマチ滑膜細胞を刺激し，炎症性サイトカインの産生を促進することが明らかとなった．更に，そのメカニズムにおいてRASF細胞質に存在するパターン認識受容体RIG-1とその補助分子が重要であることが示された．HTLV-1陽性関節リウマチの炎症病態の制御に，これら分子を標的とした新規治療について今後の研究が期待される．
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