2017 Fiscal Year Final Research Report

Maternal high fiber diet during pregnancy and lactation influences regulatory T cell differentiation in offspring in mice

Research Project

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Project/Area Number	15K08533
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Immunology
Research Institution	Juntendo University
Principal Investigator	NAKAJIMA Akihito 順天堂大学, 医学部, 非常勤助教 (30439294)
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)
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)
Project Period (FY)	2015-04-01 – 2018-03-31
Keywords	腸内細菌 / 食物繊維 / 短鎖脂肪酸 / 制御性T細胞 / 胸腺 / Aire / GPR41
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.
Free Research Field	免疫学