Gut Feelings: Intestinal Neurons Directly Control Immune Response, New Research Reveals
Lisbon, Portugal – 2024/11/22 – Scientists at the Champalimaud Foundation have discovered a direct communication pathway between the intestinal nervous system and the immune system, revealing how the gut decides whether to mount an attack against pathogens or initiate tissue repair. The breakthrough, published today, fundamentally alters our understanding of gut immunity and could pave the way for novel treatments for inflammatory bowel disease, autoimmune disorders, and even cancer.
For decades, researchers have known the gut microbiome profoundly influences immunity. However, the precise mechanisms governing this interplay remained elusive. This new study demonstrates that neurons releasing the VIP neurotransmitter within the intestine actively orchestrate immune responses by signaling to epithelial cells, which then release cytokines - proteins that act as messengers to immune cells. This finding positions the intestinal nervous system as a key decision-maker in determining the nature of the immune response.
Experiments conducted on mice by Henrique Veiga-Fernandes and his team showed that activating neurons releasing VIP triggered epithelial cells to produce cytokines that primed the body’s immune system for attack, targeting bacteria, infected cells, or tumors. Conversely,blocking the receptor for these signals resulted in a “stronger” tissue repair immune response.
Mice lacking this receptor exhibited increased susceptibility to bacterial infections like Salmonella, but displayed heightened resistance to parasitic infections. “Different immune cells have different receptors for these cytokines, so depending on which ones are released, the immune system knows whether to attack or repair,” explained Roksana pirzgalska, the study’s first author.
Researchers found cytokines essentially function as a language allowing epithelial cells to communicate with immune cells. This nuanced control suggests potential therapeutic strategies to modulate gut immunity by targeting specific neuronal pathways, offering a more precise approach than broad immunosuppression. The Champalimaud Foundation team plans to further investigate the specific types of cytokines involved and their impact on various disease models.
