Immune system with inflammatory bowel disease

The immune system in the gut of children with inflammatory bowel disease (IBD) has been mapped by researchers from Karolinska Institutet and Sachs' Children and Youth Hospital in Sweden. The findings, reported in Cell Reports Medicine, can be utilised to develop more tailored medicines.

We currently know very little about how the immune system works in children with IBD and how it varies in adults. Approximately 40 per cent of patients, including children and adults, do not respond to presently available therapies. It is therefore critical to uncover biomarkers that can both predict therapy response and aid in the discovery of novel therapeutic strategies.

"There is still no cure for inflammatory bowel disease such as Crohn's disease or ulcerative colitis, only symptomatic treatment," says Jenny Mjosberg, professor of tissue immunology at the Department of Medicine (Huddinge) at Karolinska Institutet. "IBD often first appears in early adulthood, sometimes in childhood. This study is a response to a clinical need to understand why the disease occurs and what happens in the gut in children with IBD."

Jenny Mjosberg has worked in close collaboration with colleagues at Sachs' Children and Youth Hospital and Karolinska University Hospital in Sweden to study the intestines of 25 children and eight adults with IBD, as well as ten children and eight adults without IBD. Researchers used flow cytometry and sophisticated single-cell technology, two relatively new techniques that enable the analysis of immune cells from the colon even on small biopsy samples.

The researchers found that pro-inflammatory cell types, such as innate lymphoid cells type 1 (ILC1) and cytotoxic cells, such as T cells and NK cells, were found to a greater extent in children with intestinal inflammation. But they also found that a particular subtype of protective cells - type 3 innate lymphoid cells (ILC3) - and tissue-resident T cells were present to a lesser degree in the intestinal mucosa of children with IBD.

"Inflammation seems to be linked not only to aggressive cells that drive inflammation, but also to the loss of function in the cells that help maintain a healthy gut," says Mjosberg. "The treatments that are currently available only aim to suppress inflammation, but it can be just as important to strengthen the tissue-protecting component."

Children and young people with IBD are also a valuable group to study. They are easier to catch as they just presented with symptoms and thus have not undergone any form of treatment. In addition, they are usually otherwise healthy, are non-smokers and rarely have other confounding health factors. The hope is that the results from this study can be a piece of the puzzle in the development of new treatments.

"Collaborating on this type of basic clinical research is tremendously important," says Helena Rolandsdotter, senior consultant at Sachs' Children and Youth Hospital and researcher at the Department of Clinical Science and Education, Sodersjukhuset, at Karolinska Institutet. "Our knowledge of biologic drugs and why they work or don't work is still rather poor. Biomarkers are therefore very important. In the long run, we hope to see more individually tailored treatments. This study is a step in that direction."