An explorative study for the therapeutic target in type 1 diabetes associated with pioneer transcription factor-IRF4
| Project/Area Number |
16K09756
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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 |
Metabolomics
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| Research Institution | Nagasaki University |
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Principal Investigator |
ABIRU Norio 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (00380981)
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| Co-Investigator(Kenkyū-buntansha) |
古林 正和 長崎大学, 保健・医療推進センター, 准教授 (00380874)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 1型糖尿病 / NODマウス / 転写因子 / T細胞代謝 / IRF4 / 糖尿病 / 免疫学 / 応用動物 / T細胞代謝系 |
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| Outline of Final Research Achievements |
We aimed to investigate whether pioneer transcription factor-IRF4 is involved with acquired immunity or innate immunity in the pathogenesis of type 1 diabetes. We deleted IRF4 gene from BDC2.5-TCR-NOD mouse or RAG1 knockout NOD mouse and evaluate by the adoptive transfer system from IRF4KO-BDC2.5-TCR-NOD mouse to RAG1KO NOD mouse or BDC2.5-TCR-NOD mouse to IRF4KO- RAG1KO NOD mouse. We found that disease suppression in the recipient IRF4KO- RAG1KO NOD mouse transferred with small number of naïve BDC2.5-TCR CD4+ T cells compared to wild-type RAG1KO NOD mouse. However no alteration of disease development was observed in the recipient mice transferred with large number of naïve or effector BDC2.5-TCR CD4+ T cells and wild type-RAG1KO NOD mouse indicating that IRF4 on innate immune cells plays a role to expand anti-islet autoreactive naïve CD4+ T cells in the pathogenesis of type 1 diabetes. We are now going to analyzing the phenotype in IRF4KO-BDC2.5-TCR-NOD mouse.
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| Academic Significance and Societal Importance of the Research Achievements |
IRF4を欠損したNODマウスは、膵島炎、糖尿病が完全に抑制される。しかし、IRF4は獲得免疫やT細胞代謝系、自然免疫系など広く免疫を制御している多面的転写因子であり、治療標的とした場合、免疫系全体への影響が避けられない。今回の研究では、IRF4欠損による糖尿病進展抑制機序には、自然免疫系の関与は乏しく、獲得免疫、特にT細胞代謝系への関与が推測された。
1型糖尿病の発症阻止の臨床研究では様々なreagentを用いられたが、その有効性は十分ではない。今回の我々の研究を発展させ、獲得免疫細胞でのIRF4発現の重要性、ならびにT細胞代謝系への関与が明らかになれば、新たな治療開発につながる可能性がある。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding basal bolus insulin Association between the responses of beta and alha cells to GLP1 stimulation and the glycaemic control at 6 months after switching therapy.2018
Author(s)
Horie I, Haraguchi A, Sako A, Akeshima J, Niri T, Shigeno R, Ito A, Nozaki A, Natsuda S, Akazawa S, Mori Y, Ando T, Kawakami A, Abiru N.
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Journal Title
Diabetes Res Clin Pract.
Volume: 144
Pages: 161-170
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sex differences in insulin and glucagon responses for glucose homeostasis in young healthy Japanese adults.2018
Author(s)
Horie I, Abiru N, Eto M, Sako A, Akeshima J, Nakao T, Nakashima Y, Niri T, Ito A, Nozaki A, Haraguchi A, Akazawa S, Mori Y, Ando T, Kawakami A.
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Journal Title
J Diabetes Investig
Volume: -
Issue: 6
Pages: 1283-1287
DOI
Related Report
Peer Reviewed / Open Access
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