Their findings reveal how a molecule called T-bet plays an important part in maintaining the delicate balance between a healthy immune system and healthy gut bacteria. The researchers suggest that targeting the way that T-bet affects the immune system in the gut could eventually pave the way for new ways of treating intestinal diseases such as Crohn’s disease and ulcerative colitis.
Patients with inflammatory bowel disease (IBD) can experience debilitating symptoms and serious complications such as cancer. Many patients require hospitalisation and surgery and frequently need to take medication throughout their life to keep their condition under control. Although the causes of IBD remain unknown, most research has pointed to a problem within the intestinal immune system.
Normally, the immune system in the gut provides protection from infection while happily coexisting with the trillions of harmless bacteria that live in the intestine. However, in patients with IBD, this usually protective function turns against the healthy bacteria in the gut, leading to chronic inflammation.
It has previously been shown that mice who have had T-bet removed from their immune system spontaneously develop symptoms that mimic those of IBD in humans. In this study, the team show that T-bet has a strong influence over the complex interplay between cells of the intestinal immune system: in its absence, these cells go awry, causing inflammation and ultimately IBD.
Dr Nick Powell, a Wellcome Trust Clinical Research Fellow and coauthor of the study, said: “This is the first time that the exact immune cells and molecular processes responsible for instigating IBD have been identified. Importantly, we were also able to reverse the symptoms of IBD in mice by targeting these cells, highlighting a window for therapeutic intervention in humans that should be explored.”
Professor Graham Lord, who led the research at King’s College London, said: “Inflammatory bowel diseases in various forms can be painful and debilitating illnesses. By improving our understanding of the role that T-bet plays in causing inflammation within the bowel, we will be much better placed to prevent inflammation and establish new lines of attack on these illnesses in the future.”
Investigating chronic diseases such as IBD is one of the Wellcome Trust’s core strategic research challenges.
The study is published online today in the journal ‘Immunity’.
Image: Artwork showing ulcerative colitis. Credit: Medical Art Service, Munich/Wellcome Images.
Powell N et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity 2012 (epub ahead of print).