Regenerative Medicine Utrecht

Regenerating intestine with innate lymphocytes

Graft versus host disease results from allogeneic T cells attacking host epithelial tissues. Particularly intestinal GVHD has a high morbidity and mortality despite treatment with immunosuppressive drugs. Intestinal crypt and particularly stem and Paneth cell injury appear to be at the center of this problem. Both conditioning induced damage activated molecular patterns, as well as pathogen activated molecular patterns play a role in making the mucosal barrier susceptible to immune mediated injury. While a healthy immune system can help restore epithelial barrier function through IL-22 secretion by innate lymphoid cells, this mechanism is disturbed in GVHD.

We focus on strategies to restore epithelial integrity. Human and mouse intestinal organoids are used as a model system. ILCs play a role in intestinal tissue regeneration and response to damage. Via production of IL-22 they influence recovery of stem cells. To adequately set up human cocultures with ILCs and intestinal organoids and possibly use ILCs for human therapy we want to expand human ILCs, extracted from human lymphoid tissue.

Techniques: Organoids, co-cultures, cell culture, FACS, microscopy

Contact: , Pediatric Blood and Bone marrow transplantation, Pediatric Gastroenterology lab , UMC Utrecht