| Project/Area Number |
15K08533
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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 |
Immunology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OKUMURA Ko 順天堂大学, 医学部, 特任教授 (50009700)
HABU Sonoko 順天堂大学, 医学部, 客員教授 (30051618)
MIYAKE Sachiko 順天堂大学, 医学部, 教授 (50266045)
HIRAMATSU Keiichi 順天堂大学, 医学部, 特任教授 (10173262)
WATANABE Sumio 順天堂大学, 医学部, 特任教授 (20138225)
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| Research Collaborator |
NAKANISHI Yumiko 理化学研究所, 生命医科学研究センター, 研究員 (10614274)
OHNO Hiroshi 理化学研究所, 生命医科学研究センター, チームリーダー (50233226)
HORI Shohei 東京大学, 薬学部, 教授 (50392113)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腸内細菌 / 食物繊維 / 短鎖脂肪酸 / 制御性T細胞 / 胸腺 / Aire / GPR41 / 酪酸 / 妊娠 / Treg |
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| Outline of Final Research Achievements |
Short-chain fatty acids (SCFAs) influence the immune system. We investigated the molecular mechanisms underlying regulatory T cell (Treg) differentiation in offspring regulated by a maternal high fiber diet (HFD). Plasma levels of SCFAs in offspring from HFD-fed mice were higher than those from no fiber diet-fed mice. Consequently, the offspring from HFD-fed mice had higher frequencies of thymic Treg (tTreg). We found that the offspring of HFD-fed mice exhibited higher autoimmune regulator (Aire) expression, a transcription factor expressed in the thymic microenvironment, suggesting SCFAs promotes tTreg differentiation through increased Aire expression. Notably, the receptor for butyrate, G-protein-coupled-receptor 41 (GPR41), is highly expressed in the thymic microenvironment and Aire is not increased by stimulation with butyrate in GPR41-deficient mice. Our studies highlight the significance of SCFAs produced by a maternal HFD for Treg differentiation in the thymus of offspring.
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