Neurons in the Gut Play Key Role in Regulating Inflammation

Research from Weill Cornell Medicine has unveiled a critical function of gut neurons in managing inflammation within the body. The study indicates that these neurons produce a molecule essential for modulating the immune response during inflammatory events, which could pave the way for innovative therapies aimed at treating inflammatory bowel disease (IBD) and other related conditions.

The enteric nervous system, often referred to as the body's 'second brain,' is comprised of millions of neurons responsible for essential gastrointestinal functions, including the movement of food, nutrient absorption, and blood flow regulation. Despite its known roles in these biological processes, its involvement in controlling intestinal inflammation has been less understood.

In the latest findings published in Nature Immunology, researchers focused on group 2 innate lymphoid cells (ILC2s), a type of immune cell residing in the gut lining. Previous research had established that ILC2s are significant producers of a tissue-repairing growth factor known as amphiregulin, and that these cells can respond to neuronal signals that influence their function and overall disease progression.

The current study revealed that the protective functions of ILC2s are heavily reliant on a molecule named adrenomedullin 2 (ADM2), which is secreted by neurons in the enteric nervous system. By administering ADM2, researchers were able to enhance the presence of ILC2s, offering therapeutic benefits in a preclinical model of inflammatory bowel disease. In contrast, the absence of ADM2 signaling resulted in worsened disease conditions due to a reduction in protective immune cells.

Lead researcher Dr. Jazib Uddin emphasized the significance of this finding, stating that the enteric nervous system's role in alleviating intestinal inflammation has been previously overlooked. The research suggests a previously unidentified neuro-immune interaction that could be crucial in facilitating intestinal healing.

Further investigations included translational studies involving human subjects. Analysis of tissue and blood samples from patients with inflammatory bowel disease revealed an increased expression of ADM2 compared to healthy controls. Additionally, when human ILC2s were stimulated with ADM2, they exhibited enhanced production of the tissue-protective factor amphiregulin.

These results indicate that the communication between the immune and nervous systems identified in animal models is also present in humans, underscoring the potential of the enteric nervous system as a target for therapeutic strategies against inflammatory bowel disease.

Dr. David Artis, senior author of the study, highlighted the findings as a breakthrough in understanding the complex interactions between the immune and nervous systems, particularly regarding their coordination in processes of inflammation and tissue repair. This research opens avenues for developing new therapies that could target these neuro-immune pathways.