2018 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
代謝学
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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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