Researchers map the immunology of the gut in children with IBD

Researchers map immune system in IBD to design targeted therapies.

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Inflammatory bowel disease (IBD) includes Cohn’s disease (CD) and ulcerative colitis (UC), both of which cause abdominal pain, recurrent bloody diarrhea, and, in the case of CD, occasionally growth retardation in children.

IBD can be identified by more severe symptoms and a more widespread disease at the beginning than in adults. The CD phenotype shows less isolated ileal signs and more colonic Inflammation. IBD is complex in its etiology and pathophysiology, with host genetic and environmental variables contributing to a dysregulated immune response and dysbiosis that is thought to induce chronic Inflammation.

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

Approximately 40% of patients, both children and adults do not respond to existing treatments. It is critical to uncover biomarkers that can predict treatment response and aid in discovering new therapeutic strategies.

Jenny Mjösberg, professor of tissue immunology at the Department of Medicine (Huddinge) at Karolinska Institutet, said, “There is still no cure for inflammatory bowel diseases such as Crohn’sCrohn’s disease or ulcerative colitis, only symptomatic treatment.”

Jenny Mjösberg, professor of tissue immunology at the Department of Medicine (Huddinge) at Karolinska Institutet, 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, said, “IBD often first appears in early adulthood, sometimes in childhood. This study responds to a clinical need to understand why the disease occurs and what happens in the gut in children with IBD.”

The examination of immune cells from the colon was done using flow cytometry and sophisticated single-cell technology. These two relatively recent techniques may be used for tiny biopsy samples.

The researchers discovered that children with intestinal Inflammation had higher levels of pro-inflammatory cell types, including innate lymphoid cells type 1 (ILC1) and cytotoxic cell types like T cells and NK cells.

However, they also discovered that tissue-resident T lymphocytes and a specific subtype of protective cells called type 3 innate lymphoid cells (ILC3) were, to a lower extent, present in the intestinal mucosa of children with IBD.

Mjösberg said, “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. The treatments that are currently available only aim to suppress Inflammation. However, strengthening the tissue-protecting component can be just as important.”

Children and teenagers with IBD make very interesting study subjects. They are simpler to catch because they haven’t any treatment yet and have only recently developed symptoms. Additionally, they rarely have additional complicating health conditions and are typically otherwise healthy. They also don’tdon’t smoke.

The hope is that the results from this study can be a piece of the puzzle in the development of new treatments.

Helena Rolandsdotter, the senior consultant at Sachs Children and Youth Hospital and researcher at the Department of Clinical Science and Education, Södersjukhuset, at Karolinska Institutet, said, “Collaborating on this type of basic clinical research is tremendously important, Our knowledge of biologic drugs and why they work or don’tdon’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.”

According to the study, children with IBD had fewer of a specific subtype of protective cells called type 3 innate lymphoid cells (ILC3) and tissue-resident T lymphocytes in their digestive mucosa.

This shows that the loss of function of the cells responsible for maintaining a healthy gut is also connected to Inflammation, in addition to the aggressive cells that cause Inflammation. As they only come with symptoms and have not received any treatment, children and young people with IBD are an important group to investigate.

The study was funded by the European Research Council, the European Cohn’s and Colitis Organization.

Journal Reference:

  1. Efthymia Kokkinou, Tea Soini, Ram Vinay Pandey, etal.The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis. Cell Reports Medicine. DOI: 10.1016/j.xcrm.2023.101038