Immune healing instigation leads by gut neurons post inflammation
Neuronal Signal ADM2 Promises Novel IBD Treatment
A groundbreaking study led by Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor in Immunology at Weill Cornell Medicine, has identified a significant role for Adrenomedullin 2 (ADM2) in modulating the immune response and promoting healing in inflammatory bowel disease (IBD). The findings, published in the journal Nature Immunology, suggest that ADM2 could be a promising target for new IBD therapies.
The study reveals that patients with IBD, including Crohn's disease and ulcerative colitis, have elevated expression of ADM2 compared to control individuals. This elevated expression is particularly noticeable in the enteric nervous system, which plays a crucial role in the gut's immune response.
ADM2, produced by neurons in the enteric nervous system, stimulates protective immune cells called group 2 innate lymphoid cells (ILC2s) to produce amphiregulin, a growth factor essential for healing damaged intestinal tissue. This neuro-immune interaction helps limit intestinal inflammation and promotes recovery in IBD models.
Specifically, ADM2 released from gut neurons enhances the expansion and function of ILC2s, which in turn produce amphiregulin. Therapeutic delivery of recombinant ADM2 elicits tissue-protective AREG ILC2s and limits intestinal inflammation. Conversely, loss of ADM2 signaling leads to a reduction in these protective ILC2s and worsens disease severity.
The study also finds that expression of genes encoding human ADM2 receptor (CALCRL and RAMP3) is altered in participants with IBD and associated with reduced expression of AREG in ILC2s. When human ILC2s are exposed to ADM2, they increase amphiregulin production, confirming that this mechanism operates in humans as well.
The research indicates that the immune-nervous system communication identified in mice is also present in humans. This pathway represents a neuro-immune axis that can be targeted therapeutically to restore immune balance and support tissue healing in IBD, potentially providing an alternative to broad immune suppression and its associated risks.
In summary, ADM2 serves as a neuronal signal that activates tissue-protective immune responses, promoting healing in the inflamed gut via ILC2-mediated amphiregulin production. This discovery marks a novel and promising target for IBD treatment. The enteric nervous system, previously overlooked as a therapeutic target, now emerges as a promising area for future IBD research and treatment development.
[1] Artis, D., et al. (2022). Adrenomedullin 2 promotes tissue-protective functions of ILC2s in intestinal inflammation. Nature Immunology. [2] [3] [4] [5] Data from the study.
This article is not intended to provide medical advice or replace professional healthcare. Always consult with a healthcare provider for questions about your health.
- The groundbreaking study in neuroscience news reveals that heightened neuro-immune interactions, involving Adrenomedullin 2 (ADM2), play a crucial role in the healing process of inflammatory bowel disease (IBD), especially in the context of medical-conditions like Crohn's disease and ulcerative colitis.
- In the brain of patients with IBD, ADM2, produced by neurons within the enteric nervous system, stimulates the production of amphiregulin, a growth factor critical for health-and-wellness of the intestinal tissue, by protective immune cells called group 2 innate lymphoid cells (ILC2s).
- The findings from this neuroscience research indicate that the neuro-immune axis discovered in mice is also present in humans, potentially opening new avenues in the treatment and management of IBD by targeting these interactions to restore immune balance and support tissue healing, hence promising a novel approach in IBD therapy, away from the risks associated with broad immune suppression.
