Takehito Asakawa1, Michio Onizawa2,3, Chikako Saito4, Rie Hikichi4, Daiki Yamada1, Ai Minamidate1, Tomoaki Mochimaru4, Shun-Ichiro Asahara5, Yoshiaki Kido5,6, Shigeru Oshima1, Takashi Nagaishi1, Kiichiro Tsuchiya1, Hiromasa Ohira4, Ryuichi Okamoto1, Mamoru Watanabe7. 1. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan. 2. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan. monizawa@fmu.ac.jp. 3. Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, 960-129, Japan. monizawa@fmu.ac.jp. 4. Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, 960-129, Japan. 5. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan. 6. Division of Metabolism and Disease, Department of Biophysics, Kobe University Graduate School of Health Science, Kobe, 654-0142, Japan. 7. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan. mamoru.gast@tmd.ac.jp.
Abstract
BACKGROUND: L-amino acids are the predominant forms of organic molecules on the planet, but recent studies have revealed that various foods contain D-amino acids, the enantiomers of L-amino acids. Though diet plays important roles in both the development and progression of inflammatory bowel disease (IBD), to our best knowledge, there has been no report on any potential interactions between D-amino acids and IBD. In this report, we aim to assess the effects of D-serine in a murine model of IBD. MATERIALS AND METHODS: To induce chronic colitis, naïve CD4 T cells (CD4+ CD62+ CD44low) from wild-type mice were adoptively transferred into Rag2-/- mice, after or before the mice were orally administered with D-serine. In vitro proliferation assays were performed to assess naïve CD4 T cell activation under the Th-skewing conditions in the presence of D-serine. RESULTS: Mice treated with D-serine prior to the induction of colitis exhibited a reduction in T-cell infiltration into the lamina propria and colonic inflammation that were not seen in mice fed with water alone or L-serine. Moreover, D-serine suppressed the progression of chronic colitis when administered after the disease induction. Under in vitro conditions, D-serine suppressed the proliferation of activated CD4 T cells and limited their ability to differentiate to Th1 and Th17 cells. CONCLUSION: Our results suggest that D-serine not only can prevent, but also has efficacious effects as a treatment for IBD.
BACKGROUND: L-amino acids are the predominant forms of organic molecules on the planet, but recent studies have revealed that various foods contain D-amino acids, the enantiomers of L-amino acids. Though diet plays important roles in both the development and progression of inflammatory bowel disease (IBD), to our best knowledge, there has been no report on any potential interactions between D-amino acids and IBD. In this report, we aim to assess the effects of D-serine in a murine model of IBD. MATERIALS AND METHODS: To induce chronic colitis, naïve CD4 T cells (CD4+ CD62+ CD44low) from wild-type mice were adoptively transferred into Rag2-/- mice, after or before the mice were orally administered with D-serine. In vitro proliferation assays were performed to assess naïve CD4 T cell activation under the Th-skewing conditions in the presence of D-serine. RESULTS: Mice treated with D-serine prior to the induction of colitis exhibited a reduction in T-cell infiltration into the lamina propria and colonic inflammation that were not seen in mice fed with water alone or L-serine. Moreover, D-serine suppressed the progression of chronic colitis when administered after the disease induction. Under in vitro conditions, D-serine suppressed the proliferation of activated CD4 T cells and limited their ability to differentiate to Th1 and Th17 cells. CONCLUSION: Our results suggest that D-serine not only can prevent, but also has efficacious effects as a treatment for IBD.
Authors: Rosa Reddavide; Ornella Rotolo; Maria Gabriella Caruso; Elisa Stasi; Maria Notarnicola; Chiara Miraglia; Antonio Nouvenne; Tiziana Meschi; Gian Luigi De' Angelis; Francesco Di Mario; Gioacchino Leandro Journal: Acta Biomed Date: 2018-12-17