The immune system in the intestines 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 may be used to develop more personalized drugs.
We currently know very little about how the immune system works in children with IBD and how it differs in adults. Approximately 40 percent of patients, including children and adults, do not respond to currently available therapies. It is therefore crucial to discover biomarkers that can predict response to treatment and aid in the discovery of new 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 answers the clinical need to understand why the disease occurs and what happens in the gut in children with IBD.”
Jenny Mjosberg worked closely 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.
The researchers used flow cytometry and sophisticated single-cell technology, two relatively new techniques that allow 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 type 1 cells (ILC1) and cytotoxic cells such as T cells and NK cells were found in greater numbers in children with intestinal inflammation. But they also found that a certain subtype of protective cells—innate lymphoid type 3 cells (ILC3)—and tissue-resident T cells were present to a lesser extent in the intestinal mucosa of children with IBD.
“Inflammation appears to be associated not only with aggressive cells that cause inflammation, but also with loss of function in cells that help maintain a healthy gut,” says Mjosberg. “Currently available treatments only aim to suppress inflammation, but boosting the tissue-protecting component may be just as important.”
Children and young people with IBD are also a valuable group to study. They are easier to catch because they have just shown symptoms and therefore have not undergone any form of treatment. In addition, they are usually otherwise healthy, nonsmokers, and rarely have other confounding health factors. We hope that the results of this study can be a piece of the puzzle in the development of new treatments.
“Collaboration on this type of basic clinical research is extremely important,” says Helena Rolandsdotter, senior consultant at the Sachs Hospital for Children and Youth and researcher at the Department of Clinical Science and Education, Sodersjukhuset, Karolinska Institutet. “Our understanding of biologics and why they work or don’t work is still rather poor. Biomarkers are therefore very important. In the long term, we hope to see more personalized treatments”.
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