News Releases & Research Results Elucidation of a novel anti-inflammatory mechanism created by the autonomic nervous system - New treatment for vagal infection, cancer, and inflammatory bowel diseases -

The results of collaborative research conducted by Professor Takanori Kanai, Specially Appointed Lecturer Toshiaki Teratani, and Assistant Professor Yohei Mikami of the Department of Internal Medicine (Gastroenterology and Hepatology), Professor Yuko Kitagawa of the Department of Surgery (General and Gastroenterological Surgery), Professor Hideyuki Okano of the Department of Physiology, Professor Akihiko Yoshimura of the Department of Microbiology and Immunology, Keio University School of Medicine, Professor Yusaku Iwasaki of Kyoto Prefectural University, Professor Makoto Tsuda of Kyushu University, Assistant Professor Mamoru Tanida of Kanazawa Medical University, Team Leader Takaharu Okada of the Institute of Physical and Chemical Research, Professor Masahira Hattori of the Faculty of Science and Engineering, Waseda University (at the time of the study), and Professor Masayuki Inoue of he University of Tokyo.

• For the first time in the world, this research group demonstrated the biological mechanism by which bacterial information from the intestinal tract is integrated in the liver and transmitted to the brain to control the production of intestinal regulatory T cells (pTreg*) through the vagal nerve reflex.
  *T helper cells, also called the “immunity control tower” among immune cells, which are produced mainly in the thymus and digestive tract to exert immunosuppressive effects.
• Specifically, a mouse experiment demonstrated that many antigen-presenting cells (APCs), critical for pTreg differentiation and maintenance, existed near the nerves in the intestinal mucosal lamina propria. Additionally, a neurotransmitter receptor, strongly expressed in intestinal APCs, was identified. Furthermore, mouse and human APCs, stimulated with the antigen of the receptor, showed the enhanced expressions of genes involved in pTreg differentiation and induction, revealing that signals transmitted from the nerves in the intestinal mucosal lamina propria were received through intestinal APCs to suppress the intestinal immunity.
• The results of research should facilitate the elucidation of pathophysiology and the development of new treatments for various diseases, such as modern diseases (e.g., inflammatory bowel disease, metabolic syndrome, and depression) caused by intestinal environmental changes, cancer, and gastrointestinal infections including COVID-19.

This research project was conducted with the support of the Advanced Research and Development Programs for Medical Innovation (AMED-CREST) by AMED.

The results of research were published in the scientific journal Nature on June 12.

Teratani T., et al. The liver-brain-gut neural arc maintains the Treg cell niche in the gut Nature
DOI：10.1038/s41586-020-2425-3