Epithelial injury in acute graft-versus-host disease of the gut

Suze Jansen

What was your PhD about? 

"Every year about 75 children in the Netherlands undergo an allogeneic stem cell transplantation (SCT) as an ultimate treatment for leukemia for instance. Unfortunately, often the complication acute Graft-versus-Host disease (GvHD) occurs, in which donor immune cells recognize the patients’ tissue as foreign and launch an extensive inflammatory attack. Due to the risk of dehydration, malnutrition and infection GvHD of the gut is especially dangerous.

GvHD treatment aims to suppress the overactive immune system with corticosteroids (CS), but in almost half of patients, treatment fails. The development of new therapies that do not exclusively focus on the immune system is crucial.

In my research, I show that damage to the gut lining is a major player in GvHD. Using mouse models and culture models with organoids (‘mini-guts’) and immune cells, we simulated certain aspects of GvHD. In doing so, we did 3 major discoveries:

  1. Damage to the gut lining caused by chemotherapy before SCT attracts immune cells and makes them more dangerous.
  2. Stem cells in the gut lining can be protected from damaging immune cell secretions on the tissue level.
  3. CS have the unpleasant side effect of limiting the natural regeneration of the gut lining, but treatment with interleukin-(IL)-22 stimulates the stem cells to recover the lining.

Further research using our disease models and testing our findings in human trials will hopefully lead to a better future for patients with GvHD."

What is your fondest memory of your time at RMU?  

"Definitely the themed Friday afternoon TGIF ‘borrels’ together with the Hubrecht institute, starting with the gong at 16.30u. Always a lot of fun with my colleagues!"  

What are you going to do next?  

"I will continue to work as a doctor in the pediatrics department in the hospital in Ede, and hopefully start pediatric residency sometime in 2024!"