| Project/Area Number |
15K15154
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
Huang Jun 大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (00751207)
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| Co-Investigator(Renkei-kenkyūsha) |
Ohkura Naganari 大阪大学, 医学系研究科, 特任教授 (20300949)
Tanaka Atsushi 大阪大学, 免疫学フロンティア研究センター, 特任助教 (00724105)
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| Research Collaborator |
Kitagawa Yohko
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 免疫寛容 / 自己免疫疾患 / エピジェネティクス / Regulatory T cells / epigenetics / immune tolerance / autoimmune diseases / Treg development / Epigenetic regulation / Etiology of autoimmunity / Self tolerance / Autoimmunity |
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| Outline of Final Research Achievements |
Regulatory T cells (Tregs) play an indispensable role in maintaining immune homeostasis. Understanding the molecular basis governing their development will help to understand the pathogenesis of autoimmune diseases and establish new strategies for the treatment and prevention of immunological diseases. We found that Mbd3 plays an essential role in thymic Treg development, and thus establishment of immune homeostasis. Mice with T cell-specific Mbd3 deletion have impaired Treg development, development multiple autoimmune diseases and die prematurely. Development of autoimmune diseases could be prevented by adoptive transfer of wild type Tregs. The requirement of Mbd3 for Tregs is restricted at developmental stage, since mice with Treg-specific deletion of Mbd3 could largely maintain their immune homeostasis. Our findings expand the notion that the defects in genetic and epigenetic control of thymic Tregs development could be potentially the cause of a wide range of autoimmune diseases.
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