Key research into the mysteries of inflammatory bowel disease
Researchers based in Sweden have made important progress into what causes painful gut inflammation in diseases like Crohn’s disease and ulcerative colitis. The research during the EU’s MIRA project is welcome news since, for reasons that are still unclear, globally Europe has the highest prevalence in the world of inflammatory bowel disease (IBD), according to a study published in The Lancet. Norway has the highest prevalence of ulcerative colitis, which can cause rectal bleeding, with 505 patients per 100 000. Germany leads the ranking on Crohn’s disease at 322 sufferers per 100 000. Supported by the Marie Skłodowska-Curie programme, the MIRA project shed light on the mechanisms by which certain T cells activate an immune response and acquire their functions. That could be key to understanding why some people’s immune systems fail to distinguish properly between innocuous bacteria in the gut and those needing to be resisted, causing inflammation. “We showed that activation of commensal-specific T cells happens in the lymph nodes that drain lymph from the inflamed intestines and that the function of these cells may change upon migration to inflamed tissues,” explains researcher Chiara Sorini. She was supervised by Eduardo Villablanca, Associate Professor and Wallenberg Academy Fellow in Medicine at the Karolinska Institute in Sweden, whose laboratory focuses on IBD. The research also identified dendritic cells – which act as messengers between the innate and the adaptive immune systems – as important players in inducing T cell responses. They also discovered those responses can be reprogrammed by an unknown mechanism.
“We believe the ability of commensal-specific T cells to reshape their function upon changes in the surrounding environment is one of the most intriguing discoveries of this project,” says Sorini. She believes once scientists better understand the mechanisms driving this change of function they will potentially be able to come up with ways to alleviate gut inflammation. The MIRA research included putting T cells modified to recognise microbial antigens immunodominant in IBD patients into mice. Researchers then tracked their behaviour across tissues in different experimental models of chemically induced inflammation. The team observed the T-cells’ activation in intestinal-draining lymph nodes and their migration to the intestines. They also characterised their function at different time points during the induction and resolution of inflammation. Based on their experiments, Sorini and Villablanca believe environment plays a key role in provoking the T cells’ treatment of innocuous bacterium as if it were an infectious agent. “IBD is a very complex disease resulting from the interplay of many factors, both genetic and environmental,” notes Villablanca. “However, a pre-existing disturbance of the barrier that lines the intestinal tract seems to be required for the first imprinting of commensal-specific T cells and their subsequent contribution to intestinal inflammation.” More research needs to be done into the factors causing this imbalance in the barrier lining the intestinal tract, but the MIRA team feels they have taken an important step towards tackling diseases that affected 6.8 million people in 2017, according to ‘The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017’, published in The Lancet.
MIRA, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, impaired immune responses