2020/01/14
Keio University Faculty of Pharmacy
A research group led by Associate Professor Shunsuke Kimura (Visiting Researcher at Hokkaido University Graduate School of Medical Sciences), Project Assistant Professor Yutaka Nakamura, and Professor Koji Hase of the Keio University Faculty of Pharmacy, in collaboration with Hokkaido University, has discovered a mechanism in the mouse intestine that regulates the uptake of microorganisms and antigens into the body.
Although located inside the body, the intestinal tract is connected to the outside world through the mouth. Consequently, many foreign substances and microorganisms enter the intestinal lumen along with food. Furthermore, a large number of intestinal bacteria exist, forming the gut microbiota. As a result, numerous immune cells accumulate in the intestinal tract to prevent microbial invasion. Some of the foreign substances present in the intestinal mucosa are sampled by inductive sites (Peyer's patches) in the intestine, activating the immune system as needed. This sampling of foreign substances is carried out by specialized epithelial cells called "M cells." In other words, the uptake of foreign substances by M cells is key to activating the intestinal immune response, but the mechanism for its regulation was unknown.
This research group analyzed the mechanism by which M cells are generated in the mouse intestine and discovered that Osteoprotegerin (OPG) has a role in suppressing M cell differentiation. In genetically modified mice lacking OPG, the number of M cells increased significantly. This promoted antibody production, which had the beneficial effect of suppressing the symptoms of inflammatory bowel disease. On the other hand, it is known that Salmonella, a cause of food poisoning, can invade the body through M cells. Indeed, in OPG-deficient mice, Salmonella infection increased, and resistance was markedly reduced. This indicates that while an increase in M cells activates the immune system, an excessive increase makes it easier for pathogenic microorganisms to invade through M cells, rendering the host unable to cope with the invasion of highly virulent microorganisms that cause infectious diseases. These results revealed that the regulation of M cell numbers by OPG is crucial for balancing immune activation and infection.
The results of this research were published in the online edition of the international academic journal "Nature Communications" on January 13, 2020 (U.S. Eastern Time).
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