Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine
Motoyoshi Nagai,
Takuma Okawa,
Kazuaki Nakata,
Daisuke Takahashi,
Reina Miyajima,
Hiroaki Shiratori,
Daisuke Yamanaka,
Atsuo Nakamura,
Chinatsu Oyama,
Shin-Ichiro Takahashi,
Noriko Toyama-Sorimachi,
Koichiro Suzuki,
Wakana Ohashi,
Taeko Dohi,
Yuki I. Kawamura,
Koji Hase
Affiliations
Motoyoshi Nagai
Clinical Research Advancement Section, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan; Corresponding author
Takuma Okawa
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Kazuaki Nakata
Clinical Research Advancement Section, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Daisuke Takahashi
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Reina Miyajima
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Hiroaki Shiratori
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Daisuke Yamanaka
Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Atsuo Nakamura
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan; Dairy Science and Technology Institute, Kyodo Milk Industry Co., Hinode-machi, Nishitama-gun, Tokyo, Japan
Chinatsu Oyama
Communal Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Shin-Ichiro Takahashi
Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Noriko Toyama-Sorimachi
Division of Human Immunology, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan
Koichiro Suzuki
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Wakana Ohashi
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Taeko Dohi
Clinical Research Advancement Section, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan
Yuki I. Kawamura
Clinical Research Advancement Section, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Koji Hase
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan; The Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Kanayagawa, Fukushima 960-1296, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo 108-8639, Japan; Corresponding author
Summary: Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.
