Cell Reports (Aug 2023)
The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis
- Kentaro Miyamoto,
- Tomohisa Sujino,
- Yosuke Harada,
- Hiroshi Ashida,
- Yusuke Yoshimatsu,
- Yuki Yonemoto,
- Yasuhiro Nemoto,
- Michio Tomura,
- Hassan Melhem,
- Jan Hendrik Niess,
- Toshihiko Suzuki,
- Toru Suzuki,
- Shohei Suzuki,
- Yuzo Koda,
- Ryuichi Okamoto,
- Yohei Mikami,
- Toshiaki Teratani,
- Kenji Tanaka,
- Akihiko Yoshimura,
- Toshiro Sato,
- Takanori Kanai
Affiliations
- Kentaro Miyamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Miyarisan Pharmaceutical Co., Ltd., Research Laboratory, 1-10-3, Kaminagazato, Kita-ku, Tokyo 114-0016, Japan
- Tomohisa Sujino
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding author
- Yosuke Harada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Hiroshi Ashida
- Department of Bacterial Infection and Host Response, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Medical Mycology Research Center, Chiba University, 1-8-1, Inohana, Cyuo-ku, Chiba city, Chiba 260-8673, Japan
- Yusuke Yoshimatsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Yuki Yonemoto
- Department of Gastroenterology and Hepatology, Tokyo Medical Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
- Yasuhiro Nemoto
- Department of Gastroenterology and Hepatology, Tokyo Medical Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
- Michio Tomura
- Laboratory of Immunology, Faculty of Pharmacy, Osaka Otani University, 3-11-1 Nshikiorikita, Tondabayshi, Osaka, 584-8584, Japan
- Hassan Melhem
- Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
- Jan Hendrik Niess
- Department of Biomedicine, University of Basel, 4031 Basel, Switzerland; Clarunis-University Center for Gastrointestinal and Liver Diseases, University Hospital Basel, 4002 Basel, Switzerland
- Toshihiko Suzuki
- Department of Bacterial Infection and Host Response, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
- Toru Suzuki
- Division of Brain Sciences Institute for Advanced Medical Research, Keio University School of Medicne, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Shohei Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Yuzo Koda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
- Yohei Mikami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Toshiaki Teratani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Kenji Tanaka
- Division of Brain Sciences Institute for Advanced Medical Research, Keio University School of Medicne, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Akihiko Yoshimura
- Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Toshiro Sato
- Department of Organoid Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; AMED-CREST, Japan Agency for Medical Research and Development, 1-7-1, Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 8
p. 113005
Abstract
Summary: The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.
