MADRID, 18 (EUROPA PRESS)
A team of researchers from Weill Cornell Medicine (United States) has discovered that targeting intestinal neurons can help combat inflammation, as they produce a molecule that is "fundamental" in shaping the intestinal immune response during and after inflammation.
“The enteric nervous system has long been neglected when thinking about how we can resolve harmful intestinal inflammation (…) Our work suggests that there may be a previously unknown neuroimmune mechanism that drives intestinal healing responses,” said lead author and Ruth L. Kirschstein postdoctoral fellow at the National Institutes of Health at Weill Cornell Medicine, Dr. Jazib Uddin.
Although the enteric nervous system is known to regulate essential functions of the intestine, less known are its actions in controlling inflammatory responses in the intestine.
That's why the work, published in the journal 'Nature Immunology', has focused on group 2 innate lymphoid cells (ILC2), immune cells that reside in the intestinal lining and are an "important" source for healing tissues, as they have the ability to receive neuronal signals that modulate their function and can affect disease progression and recovery.
The article also demonstrated that the tissue-protective function of ILC2s depends on the production of the enteric nervous system molecule adrenomedullin 2 (ADM2). Administration of the molecule expanded this ILC2 pool and provided a therapeutic benefit in a preclinical model of inflammatory bowel disease; meanwhile, loss of ADM2 signaling exacerbated the disease due to the lack of these protective cells.
On the other hand, researchers have conducted translational studies in patients with inflammatory bowel disease, through the analysis of human tissue and blood samples from the Living Cell Bank of the Jill Roberts Institute for Inflammatory Bowel Disease Research at Weill Cornell Medicine.
This analysis revealed that these patients had elevated ADM2 expression compared to control subjects, revealing that ADM2-stimulated human ILC2s directly promoted the production of amphiregulin, a tissue-protective gene.
All of these findings suggest the existence of communication between the immune system and the nervous system in humans, which in turn identifies the enteric nervous system as a promising therapeutic target for inflammatory bowel disease.
"The findings of this current study provide new insights into how the immune and nervous systems 'talk' to each other and coordinate complex processes, including inflammation and tissue repair, and offer the potential for novel therapies targeting these neuroimmune interactions," said senior study author Dr. David Artis.
Artis also serves as director of the Jill Roberts Institute for Inflammatory Bowel Disease Research, the Michael Kors Professor of Immunology at Weill Cornell Medicine, and is co-director of the Allen Discovery Center for Neuroimmune Interactions.
This research was supported in part by the Jill Roberts Institute for Inflammatory Bowel Disease Research, the Kenneth Rainin Foundation, the Sanders Family Foundation, the Rosanne H. Silbermann, Linda and Glenn Greenberg Foundation, the Allen Discovery Center Program, a program advised by the Paul G. Allen Frontiers Group of the Paul G. Allen Family Foundation, and the National Institutes of Health.
