More than 4000,000 people in Germany are affected by the chronic inflammatory bowel diseases Morbus Crohn or ulcerative colitis. Patients often suffer from flare-ups, which damage intestinal tissue. In spite of tremendous advances in treating the diseases with medication, the chronic inflammation still cannot be kept sufficiently in check for a number of patients. Until now, little has been known about what actually causes flare-ups.  Researchers have now proven that certain cells in the intestines have a key role to play in inducing acute inflammatory episodes. It is hoped that this discovery will lead to innovative approaches to treating the diseases in future.

Chronic inflammatory diseases are caused by a complex mixture of various factors. This leads eventually to the intestine's immune system becoming over-stimulated, with the resulting inflammation often leading to serious symptoms of disease. The immune system in the intestines includes cells known as tissue resident memory cells, or TRM cells for short. So far, scientists were unaware of the part these cells had to play in causing chronic inflammation in the intestines.

A team of researchers have now successfully deciphered these mechanisms. The researchers were able to prove, for example, that TRM cells have a highly inflammatory potential, and appear to induce flare-ups. The data also suggest that TRM cells regulate the migration and differentiation of other immune cells and therefore have a central role to play in regulating the immune response. Accordingly, patients with a high proportion of TRM cells in their intestinal lining have a greater risk of suffering from acute inflammatory episodes than those with a lower proportion.

Pro-inflammatory T_RM cells accumulated in the mucosa of patients with IBD, and the presence of CD4⁺CD69⁺CD103⁺T_RM cells was predictive of the development of flares. In vivo, functional impairment of T_RM cells in mice with double knockout of the T_RM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system.

Finally, authors show that depletion of T_RM cells led to a suppression of colitis activity. Together, these data demonstrate a central role for T_RM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.

'Until now, no-one realised that TRM cells have a role to play in immunological diseases,' explains the author. 'We believe that our findings are also of relevance for other chronic inflammatory diseases.' In addition, the researchers hope that their discovery will form the basis for treating diseases in future. 'Future treatments may well be based on the important role TRM cells have to play in the chronic inflammation of the intestine,' predicts another author, 'by taking early action, we may be able to suppress the disease or flare-ups of the condition.'

https://www.fau.eu/2019/01/28/news/cells-that-destroy-the-intestine/

https://www.nature.com/articles/s41590-018-0298-5