UEG Week is Europe’s largest and most prestigious annual congress for digestive health. It brings together experts from around the world to share the latest research updates.
How do immune cells damage the gut?
In coeliac disease, special immune cells called intraepithelial lymphocytes (IELs) become inappropriately activated in response to gluten, causing them to multiply and attack other cells in the lining of the gut.
One important driver of this process is a signalling protein called interleukin-15 (IL-15), which helps control the activity and behaviour of IELs. In coeliac disease, IL-15 can be produced at abnormally high levels which activates enzymes inside the IELs called PIM kinases (PIM1 and PIM2). These activated enzymes contribute to the damaging activity of IELs, triggering them to release toxic signals to damage the surrounding cells that form the gut lining.
What has Professor Swamy’s research found?
Professor Swamy’s team has found higher levels of the enzymes PIM1 and PIM2 in the intestinal biopsies of people with coeliac disease, particularly within the IELs. This supports the concept that PIM kinases play a key role in contributing to damage to the gut lining seen in coeliac disease. Crucially, the team has found that molecules called inhibitors can bind to PIM kinases and block their activity, disrupting the signals that drive IELs to damage the gut lining. This raises the question of whether PIM kinases could be targeted to help prevent intestinal damage in coeliac disease.
What does this research mean for people living with coeliac disease?
These findings point towards a potential new avenue for developing treatments for coeliac disease. Treatments that block these enzymes are already being explored in other conditions, including certain types of cancers and rheumatoid arthritis, providing a useful starting point for exploring their application in coeliac disease. Further research is needed to establish whether blocking PIM kinases can safely and effectively prevent intestinal damage in people with coeliac disease.
Currently, the only established treatment for coeliac disease is a strict, lifelong gluten free diet. Research into new targets is an important part of the search for additional treatment options that could one day help people manage the condition.
By uncovering the mechanisms that drive intestinal damage, Professor Swamy and her team hope to move closer to identifying new ways to protect the gut in coeliac disease.
Dr Swamy said: “When I present my research findings on coeliac disease, many patients tell me they’d be much happier if they could avoid feeling sick when they accidentally eat gluten. I’m excited by the possibility that this idea, born out of basic research findings in my lab, may eventually lead to a potential treatment for coeliac disease. I am thrilled to partner with Dr Penny and Professor Sanders from the National Centre for Refractory Coeliac Disease in Sheffield, and with Coeliac UK, to work towards making this possibility a reality.”