| Project/Area Number |
15K08107
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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 |
Medical pharmacy
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| Research Institution | Juntendo University |
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Principal Investigator |
IKEDA Keigo 順天堂大学, 医学部, 准教授 (40465068)
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| Co-Investigator(Kenkyū-buntansha) |
関川 巖 順天堂大学, 医学部, 助教授 (80179332)
佐藤 実 産業医科大学, 産業保健学部, 教授 (90162487)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKASAKI Yoshinari 順天堂大学, 医学部, 教授 (80154772)
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| Research Collaborator |
HAYAKAWA Kunihiro 順天堂大学, 大学院環境医学研究所
FUJISHIRO Maki 順天堂大学, 大学院環境医学研究所
KAWASAKI Mikiko 順天堂大学, 大学院環境医学研究所
SUZUKI Satoshi 順天堂大学, 大学院環境医学研究所
MIYASHITA Tomoko 順天堂大学, 大学院環境医学研究所
HIRAI Takuya 順天堂大学, 大学院環境医学研究所
TSUSHIMA Hiroshi 順天堂大学, 大学院環境医学研究所
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 全身性エリテマトーデス / JAK阻害薬 / Ｉ型インターフェロン / IFIT3 / T細胞 / Ⅰ型インターフェロン / ISG15 / インターフェロン |
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| Outline of Final Research Achievements |
We evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE in this research project. We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4+ T cells (SLE mice) and CD3+ T cells (human SLE patients) were measured by DNA microarray and qRT-PCR. TOFA treatment resulted in reduced levels of anti-dsDNA antibodies, decreased proteinuria, and amelioration of nephritis as compared with those observed in control animals. We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively. Our results suggest that TOFA could be utilised for the development of new SLE-specific therapeutic strategies.
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