A recent study by Weill Cornell Medicine uncovers that neurons in the gut produce adrenomedullin 2 (ADM2), which plays a vital role in regulating immune responses during inflammation, opening new avenues for treating inflammatory bowel disease (IBD).

Experiments indicate that blocking ADM2 signaling worsens disease outcomes, while administering ADM2 reduces inflammation and promotes recovery, underscoring its protective role.

When ADM2 is given in preclinical models, it enhances ILC2 activity and tissue healing, whereas loss of ADM2 signaling diminishes protective ILC2s and aggravates disease severity.

Studies involving human tissue and blood samples from IBD patients reveal elevated ADM2 levels compared to controls, with human ILC2s responding to ADM2 by increasing amphiregulin production, suggesting similar neuro-immune interactions in humans.

Published in Nature Immunology, the research confirms that the neuro-immune pathway identified in mice is also present in humans, indicating potential for ADM2-based therapies to treat gut inflammation and enhance tissue repair.

The study demonstrates that this neuro-immune communication exists in both mice and humans, with IBD patients showing higher ADM2 levels and ILC2s reacting to ADM2 with increased amphiregulin output.

The enteric nervous system, often called the 'second brain,' contains hundreds of millions of neurons and is now shown to influence intestinal inflammatory responses through immune cells known as ILC2s.

The research shows that ADM2 encourages the growth of type 2 innate lymphoid cells (ILC2s), which release tissue-healing factors like amphiregulin, thereby supporting intestinal repair.

These findings highlight that the enteric nervous system actively controls intestinal inflammation and healing, revealing promising targets for IBD therapy through neuro-immune interaction modulation.