Vagus nerve-mediated intestinal immune regulation: therapeutic implications of inflammatory bowel diseases

Author:

Mikami Yohei1ORCID,Tsunoda Junya2,Kiyohara Hiroki1,Taniki Nobuhito1,Teratani Toshiaki1,Kanai Takanori13

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

2. Department of Surgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

3. AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan

Abstract

Abstract The pathophysiology of inflammatory bowel diseases (IBDs) involves immunological, genetic and environmental factors. Through its ability to sense environmental stimuli, the autonomic nervous system plays a key role in the development and persistence of IBDs. The vagus nerve (VN), which contains sensory and motor neurons, travels throughout the body to innervate the gut and other visceral organs in the thoracic and abdominopelvic cavities. Recent studies show that the VN has anti-inflammatory effects via the release of acetylcholine, in what is known as the cholinergic anti-inflammatory pathway (CAIP). In the gut immune system, the CAIP is proposed to be activated directly by signals from the gut and indirectly by signals from the liver, which receives gut-derived bioactive substances via the portal vein and senses the status of the gut. The gut–brain axis and liver–brain–gut reflex arc regulate a wide variety of peripheral immune cells to maintain homeostasis in the gut. Therefore, targeting the neural reflex by methods such as VN stimulation is now under investigation for suppressing intestinal inflammation associated with IBDs. In this review, we describe the role of the VN in the regulation of intestinal immunity, and we discuss novel therapeutic approaches for IBDs that target neuroimmune interactions.

Funder

Japan Society for the Promotion of Science

Advanced Research and Development Programs for Medical Innovation

Takeda Science Foundation

Kanae Foundation for the Promotion of Medical Science

Mishima Kaiun Memorial Foundation Research

Yakult Bio-Science Foundation

Keio University Medical Fund

Publisher

Oxford University Press (OUP)

Subject

Immunology,General Medicine,Immunology and Allergy

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