Getting into the guts of inflammatory bowel diseases There is currently no cure for inflammatory bowel diseases, a group of conditions that includes ulcerative colitis and Crohn’s disease. Recent studies have shown that early, complete mucosal healing in the gut leads to improved patient prognosis, now Dr Annika Frede and her colleagues are probing deeper into the underlying mechanisms behind the process. A group of diseases which affect the gastrointestinal tract, the inflammatory bowel diseases (IBD) can seriously affect a patients’ quality of life, with symptoms including severe diarrhea, abdominal pain, loss of appetite and weight loss, as well as tiredness. The two main diseases under the wider umbrella of IBD are Crohn’s disease and ulcerative colitis, and while they are distinct from each other they share some common features. “The two diseases are generally described as inflammation of the bowel, but they can involve inflammation of the whole gastro-intestinal tract, starting even from the mouth,” says Dr Annika Frede, a postdoctoral student at the Karolinska Institute in Sweden. “IBD is a group of chronic diseases which have acute phases, followed by periods of remission.” The majority of patients with IBD are currently treated using anti-inflammatory drugs or antibiotics, both of which are targeted at the inflammatory phase of the condition. However, clinical studies have shown that patients who experience gut mucosal healing relatively soon after the onset of IBD have a better long-term prognosis, an area of great
Cross-sections of murine colonic tissue during homeostasis (left, “healthy”) and chemically-induced inflammation (right, “inflamed). The tissue is enlarged during inflammation and shows cell infiltrates. Furthermore, the typical crypt structure as well as the layer of epithelial cells is impaired.
and leads to inflammation. When we take this chemical away the mice recover – we are trying to understand how this recovery happens,” she outlines. The wider aim is to help accelerate gut mucosal healing in the recovery phase of IBD, or to start it earlier. “We have found that in this recovery phase the population of B-cells increases markedly,” says Dr Frede.
We feed the mice a chemical which disrupts the epithelial barrier, and leads to inflammation. When we take this chemical away the mice recover. interest to Dr Frede. “Mucosal healing is generally defined as the resolving of ulcers that occur in the gut,” she explains. “In IBD the intestinal epithelium – a layer of cells which protects the interior of the body from whatever travels through the gastro-intestinal tract – is disrupted, leading to inflammation. Through gut mucosal healing, this epithelial layer can be effectively closed again.”
Gut mucosal healing This could hold important implications in terms of IBD treatment, yet the focus at this stage in Dr Frede’s research is more on the underlying mechanisms behind gut mucosal healing. Many cell types are involved in gut mucosal healing, now Dr Frede and her colleagues are using a chemical induced mouse model of colitis to investigate the role of these different cells. “We feed the mice a chemical which disrupts the epithelial barrier,
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Researchers are investigating several of the different cell types involved in gut mucosal healing, including B-cells. These B-cells have two main functions, namely the secretion of antibodies and the activation of certain other cells, yet there are a lot of different B-cell subgroups which are yet to be fully described, another important dimension of Dr Frede’s research. “We are investigating whether there is one specific group of B-cells which helps in tissue repair,” she outlines. The primary focus in this research is IBD, yet it could also hold wider relevance to tissue repair in other parts of the body. “It could help us to understand tissue repair in other mucosal sites, the lung for instance,” says Dr Frede. “At the moment, our research is about building a deeper understanding of gut mucosal healing.” This mainly involves the use of mouse models at this stage, yet Dr Frede is keen to also analyse samples of human tissue in future, from
which wider conclusions can then be drawn. “We want to see if what we find in mice holds true in humans,” she says. While this research is currently exploratory in nature, the longerterm objective is to translate it into improved treatment of IBD. “We want to use our research to help design therapies,” continues Dr Frede. The role of antigen presenting cells in gut mucosal healing following inflammation Eduardo Villablanca (Principal Investigator) Annika Frede Ph.D., Department of Medicine Solna, Karolinska Institutet, Villablanca lab, Immunology and Allergy Division 17176 Stockholm Karolinska vägen L8:03 T: +46 738028510 E: annika.frede@ki.se W: ki.se W: https://ki.se/en/meds/ research-group-eduardovillablanca-immunologyand-allergy Dr. Annika Frede is a postdoctoral fellow in the group of Eduardo Villablanca at the Karolinska Institute since 2017. She focusses her research on understanding the aetiology of inflammatory bowel disease as well as healing processes in the gastrointestinal tract. Before conducting her research in Stockholm she gained her Ph.D. in 2016 on nanoparticle-based siRNA delivery to modulate inflammatory responses.
German Research Foundation
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