For the first time in the world, a group led by Keio University has revealed that the liver integrates information on intestinal bacteria and transmits it to the brain, and the production of intestinal regulatory T cells is regulated through the vagal reflex.
In the intestinal tract, intestinal homeostasis is maintained by the action of peripheral regulatory T cells (pTreg) that suppress excessive immune responses.On the other hand, recent studies suggest that autonomic nerves may be involved in intestinal immune disorders, but the relationship between the nervous system and intestinal pTreg was unclear.
In this study, we first discovered that in mice, many antigen-presenting cells (APCs), which are extremely important for the differentiation and maintenance of intestinal pTreg, are present in the vicinity of nerves in the intestinal lamina propria.Furthermore, we found that the neurotransmitter receptor acetylcholine receptor is highly expressed in the intestinal APC, and that stimulation of this enhances the expression of genes involved in the differentiation and induction of pTreg.
Next, an experiment was conducted to artificially block the vagus nerve of mice.As a result, gene expression enhanced via intestinal APC was impaired, intestinal pTreg was significantly reduced, and the pathological condition was exacerbated in enteritis model mice.
Therefore, when we searched for a neural circuit connecting the intestinal tract and the brain, we found that the vagus nerve in the liver was activated in mice that developed colitis.A closer examination of the relationship between the nervous system and the intestinal pTreg reveals that the vagus nerve, which transmits information from the liver to the brain, transmits stimuli to the brain stem and activates the intestinal APC by nerve reflexes via the vagus nerve, which transmits stimuli from the brain to the intestine. I understand.In other words, there is a mechanism in which the liver accumulates and integrates information on the intestinal environment, transmits it to the brain via the autonomic nervous system, and feeds back appropriate commands from the brain to the intestine so that intestinal immunity is not excessively activated. It became clear.
This discovery will lead to the development of new treatments for various diseases such as inflammatory bowel disease, metabolic syndrome, depression, cancer, and gastrointestinal infections including COVID-19, which are attributed to the disturbance of the intestinal environment. Be expected.
Paper information:[Nature] The liver-brain-gut neural arc maintains the Treg cell niche in the gut
