Goblet cells as regulators of colonic immunity: implications for the pathogenesis of colitis

Ulcerative colitis (UC) is a chronic disease with unknown etiology.

The current understanding of UC is that the inflammation targets gut bacteria, but detailed understanding of why patients react to their microbiota with an inflammation is 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 currently unknown 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 during health and disease.

We 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 we will use imaging techniques, flow cytometry and mass spectrometry.

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. This project will be performed at the department of physiology, University of Gothenburg.