Crohn’s & Colitis Congress™

Sessions Speakers Exhibitors Floor Plan Buzz

P094 - PROINFLAMMATORY RESPONSES OF THE INTESTINAL EPITHELIUM ARE PREDOMINANTLY FACILITATED BY STEM CELLS (Room Poster Hall)

Background: A disturbed balance between reactivity and tolerance of the intestinal epithelium (IE) to bacterial compounds is one of the key contributors to the IBD pathogenesis. To date, research has mainly focused on the epithelial responses in general, whereas individual roles of different epithelial subsets (including stem cells, Paneth-like cells, neuroendocrine cells, enterocytes etc.) and the dynamics of their responses have not been completely addressed. Methods: To understand the dynamics of the epithelial immune responses to bacteria and to recognize the individual roles of different cell types in the intestinal epithelium, we used primary intestinal epithelial cultures (intestinal organoids). In contrast to other model systems used before, the organoids contain all the cell types and their progenitors present in the intestinal epithelium and are functionally stable during long term culture. We have characterized the epithelial immune response of intestinal organoids to soluble bacterial lysates using single cell transcriptomics - a method that allows us to measure the expression of all genes in a single cell. Results: Our findings show that: 1. Intestinal organoids retain their capability to respond to stimulation with bacterial lysates by upregulation of pro-inflammatory genes. 2. Prolonged exposure leads to a continuous decline in cytokine production, downregulation of stem cell markers, growth impairment and upregulation of differentiation markers; all of which is reversible after the removal of the bacterial stimulus. 3. Single cell transcriptomics revealed that the cell’s capacity to express pro-inflammatory genes positively correlates with the presence of known stem cell markers and declines with the expression differentiation markers. 4. Expression levels of pro-inflammatory cytokines are highly unequal among individual stem cells. Conclusion: Stem cells are the main source of proinflammatory signals upon epithelial exposure to bacteria