Building tolerance to gut bacteria: role of epithelial - immune interactions

Ulcerative colitis (UC) is a disease of unknown etiology.

The current understanding of UC is that the inflammation targets gut bacteria, but detailed understanding of why tolerance to the microbiota is lost currently lacking.

Despite this knowledge gap it is clear that inappropriate interactions between the microbiota and the epithelium caused by mucus barrier defects triggers disease.

Why the colon is unable to handle direct contact between the epithelium and the microbiota is not known but a discovery showing that mucus secreting goblet cells (GCs) sample luminal antigens and deliver them to the immune system may be one factor that links mucus defects to colitis. This proposal aims to explore the role of epithelial immune interactions in regulation of the colonic barrier.

I will explore how GCs communicate with the immune system, evaluate how mucus defects affects GC mediated regulation of gut immunity, and translate findings from experimental models to human physiology and pathophysiology. To adress these points I will use imaging techniques, flow cytometry, mass spectrometry and RNAseq.

Completion of this proposal will increase our understanding of how we live in symbiosis with our microbiota, and provide novel avenues of therapy for UC.

The significance of this work is that it span the entire process from antigen uptake by GCs to induction of adaptive immune responses. This work will be performed at the dept. of physiology, University of Gothenburg.