Crohn's Disease: A Mechanism Behind the Disease Discovered

From today we know a new mechanism that seems to be at the basis of the inflammation typical of chronic intestinal diseases, such as Crohn's disease and ulcerative colitis, and that could become the target of new therapies. The discovery is due to an Italian study published in the Journal of Clinical Investigation and which involved several centers of excellence for gastroenterology .

How the newly discovered mechanism works

We are talking about the Tmem219 receptor, which is present at very high levels in the intestine of patients with chronic inflammatory bowel disease, and whose activation would cause, according to the results of the research, the death of the intestinal stem cells that express it.

“The death induced by Tmem219 activation on intestinal stem cells aggravates intestinal damage and prevents healing,” explained Paolo Fiorina of Fatebenefratelli-Sacco Hospital, who took part in the study. This damage in turn contributes to increasing the permeability of the intestinal mucosa and enhances the local inflammatory response, promoting the recruitment of immune cells. Although it is not clear what gives rise to these diseases, one hypothesis is that they are linked precisely to unregulated activation of the immune response.

The study on patients and animal models

The authors of the study examined intestinal tissue samples taken from patients with Crohn's disease in different stages, as well as from healthy people. The comparison showed that patients with the disease in the acute phase have a reduced number of intestinal stem cells, unlike those who are in remission. The reduction in intestinal stem cells is due to their death, induced by the activation of the Tmem219 receptor. The researchers then tested the effects of its inhibition pharmacologically or through gene editing techniques in mice with Crohn's disease. The results seem promising, since both approaches seem to prevent damage due to the disease and protect the intestinal mucosa in animal models, restoring the ability to regenerate.

Regenerate damaged mucosa

The possibility of achieving the regeneration of damaged mucosa opens the way to new therapeutic strategies for patients with Crohn's disease and ulcerative colitis, especially for those with more severe disease who do not respond to standard therapy with immunomodulatory drugs, commented Giovanni Maconi of the University of Milan, director of Gastroenterology at Fatebenefratelli-Sacco. Of course, it is still a long road: further studies will be needed to identify any active molecules and test their safety and efficacy in humans.