2017 Fiscal Year Final Research Report

The establishment of novel treatment for systemic lupus erythematosus using JAK inhibitor

Research Project

PDF

Project/Area Number	15K08107
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Medical pharmacy
Research Institution	Juntendo University
Principal Investigator	IKEDA Keigo 順天堂大学, 医学部, 准教授 (40465068)
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)
Co-Investigator(Renkei-kenkyūsha)	TAKASAKI Yoshinari 順天堂大学, 医学部, 教授 (80154772)
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
Project Period (FY)	2015-04-01 – 2018-03-31
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
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.
Free Research Field	リウマチ学、免疫学、臨床薬理学