Immune cell networks in Inflammatory Bowel Disease: towards novel therapeutic approaches

Abstract

Inflammatory bowel disease (IBD), comprising of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract characterized by a relapse-remitting disease course. Although treatment options—such as biologics and small molecule therapies—have expanded, many patients still experience poor or diminishing responses and side effects. This variability in how patients respond to treatment might be due to differences in the underlying biology of their disease. Currently, IBD treatment follows a "one-size-fits-all" approach. Comprehensive profiling of the cellular immune system in IBD enhances patient classification and might aid in the development of personalized strategies. In this thesis, we applied multidimensional technologies, such as single-cell mass cytometry, imaging-mass cytometry and spectral flow cytometry on intestinal tissue, fistula scraping and blood samples from patients with IBD and controls to gain a more comprehensive understanding of the immunological components involved in this disease. We also explored the microbial composition of perianal fistulas to distinguish between CD-associated and cryptoglandular fistulas. In patients with ulcerative proctitis, we investigated the local injection of allogeneic mesenchymal stromal cells (MSCs) as a novel therapy. MSC treatment was found to be safe, feasible, and associated with changes in the tissue immune environment.