| Project/Area Number |
17K10084
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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 |
Pediatrics
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Tajima Asako 東京慈恵会医科大学, 医学部, 講師 (00328337)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 1型糖尿病 / 自己免疫 / ICA69 / 自己免疫破綻 / ノックアウトマウス / 自己免疫疾患 |
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| Outline of Final Research Achievements |
Patients with type 1 diabetes develop other autoimmune disorders more frequently than those without diabetes, however, the pathophysiology remains unclear. Recent studies have indicated the failure of immune tolerance due to the suppression of antigen expression in the thymus as a possible mechanism for the development of autoimmunity. In this study, we have investigated whether ICA69, one of the autoantigens for type 1 diabetes, contributes in the acceleration of the onset of diabetes or in the induction of extrapancreatic autoimmune diseases. Earlier onset of diabetes was noted in the heterozygotic ICA69 knockout mice than in the wild type in female mice, while the male wild type mice developed hyperglycemia earlier than the heterozygotic ICA69 knockout mice. Hematoxylin and eosin stain showed a lymphocytic invasion of pancreatic islets even before the progression of hyperglycemia. There was no clear difference in the level of invasion between the wild type and the heterozygotes.
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| Academic Significance and Societal Importance of the Research Achievements |
1型糖尿病に複数の自己免疫疾患が発症しやすい原因や、自己免疫疾患がなぜ女性に多くみられるかに関してはまだ解明されていない部分が多い。これまでの研究により、ICA69が１型糖尿病を初めとする自己免疫疾患の発症に関与することや、ゴルジ体でのインスリン産生に関わることが報告されている。本研究は、ICA69に対する免疫寛容の破綻を人工的に引き起こし、1型糖尿病のみならず複数の自己免疫疾患の発症が誘導されるかを検証することを目的とした。これらの病態におけるICA69の役割を検討することは、APS2型、3型も含めた複数の自己免疫疾患の発症機序の解明に寄与すると思われ、学術的に大きな意味を持つ。
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