A novel system to study intestinal lymphocytes

The maintenance of intestinal homeostasis, which depends on a delicate balance between the immune system, the intestinal epithelium and the gut microbiota, has local and systemic implications for health, and gut inflammation contributes to multiple diseases, including inflammatory bowel disease (IBD).

I propose to validate a novel in vitro system that mimics the gut microenvironment and enables detailed mechanistic studies on the crosstalk between lymphocytes, the epithelium and the microbiota. Innate lymphoid cells (ILCs) have been shown to regulate intestinal homeostasis and inflammation and the epithelium and the microbiota interact closely with ILCs, controlling their differentiation and function. I will characterise the molecular interactions between ILCs, the epithelium and the microbiota. My pilot data show that three-dimensional cultures of intestinal epithelial cells (IECs), called intestinal organoids, support the development of ILCs. I propose to fully characterise the ILCs that develop in these co-cultures and to identify and validate key molecular pathways mediating the crosstalk between ILCs, IECs and the microbiota.

This will form the basis for larger studies and grant applications. Such studies are an essential foundation for future efforts aiming to manipulate interactions between these three compartments in order to promote intestinal homeostasis.