New therapeutic options for IBD in childhood

Researchers at Trinity College Dublin (TCD) have identified potential new therapeutic options for inflammatory bowel (IBD) disease in children.

Around 40,000 people in Ireland have IBD, symptoms of which can include abdominal pain, persistent diarrhoea, weight loss and fatigue. Some 25% of those affected first experience the condition in childhood.

While the exact cause of IBD is unknown, TCD researchers working with paediatric gastroenterologists at CHI Crumlin have previously shown that small proteins known as IL-36 cytokines are ‘switched on’ in the inflamed intestines of children with newly diagnosed IBD. It is still not fully understood how IL-36 cytokines drive disease, however this latest research addresses this.

The researchers have demonstrated how IL-36 can instruct pro-inflammatory CD4+ T cells to accumulate in the inflamed intestine and worsen disease. They essentially act as an instructive signal to drive inflammation in different tissue sites, playing a major role in driving the inflammation seen in IBD.

Il-36’s activity is perhaps best characterised in the skin where it is thought to play an important role in driving chronic inflammation in diseases such as psoriasis. Normally the activity of IL-36 is tightly regulated in healthy tissues to ensure that inappropriate activity does not result in chronic inflammation. However, this regulation appears to be lost in IBD.

The key finding of this study identifies how IL-36 can cause the accumulation of the damaging CD4+ T cells in the inflamed intestine, where they play a central role in driving the inflammation observed in IBD. These findings build upon the reseachers’ earlier work which identified that IL-36 cytokines were elevated among children with IBD and this was associated with worsening disease outcomes.

Identifying how these proteins promote disease progression will be invaluable in advancing efforts to target their activity among IBD patients as a new therapeutic option, the researchers noted.

“These results shed new light on how a potential new therapeutic target can promote the early pathogenesis of IBD. Gaining a deeper understanding of how IBD develops during its earliest stages, in childhood and adolescence, is critically important in efforts to design new and improved treatment options for these patients as they transition to adulthood,” explained Patrick Walsh, associate professor in paediatric immunology at TCD’s School Of Medicine.

The study is published in the journal Mucosal Immunology.