2nd Annual BMRP Investigator Meeting - Abstract

 Role of the Follicle-Associated Epithelium in the Initiation of Inflammatory Bowel Disease

Johan D. Söderholm1,a, Ann-Charlott Ericson1, Karl-Eric Magnusson2 and Per Artursson3

1Department of Biomedicine and Surgery, 2Dept of Microbiology, Linköping University (Sweden); 3Department of Pharmacy, Uppsala University (Sweden)

The earliest visible signs of Crohn’s disease are microscopic erosions at the follicle-associated epithelium (FAE), covering Peyer’s patches.  The FAE, with its enrichment in M cells, is important for regulation of mucosal immune responses and as a route of entry for micro-organisms.  Our aim is to study the interaction between microorganisms, epithelial cells and immune cells in the FAE, to add new insights into the pathophysiology of inflammatory bowel disease (IBD).

  • Chronic stress induced a pronounced increase in FAE uptake of antigens and bacteria in rat ileum.  As a consequence of enhanced antigen uptake in the FAE, an exaggerated delayed-type hypersensitivity response and altered proportions of CD4+ T cells in the spleen were seen.
  • To identify proteins suitable as markers for human FAE and M-cells and targets for drug delivery to these sites, an in vitro model of the FAE (co-culture of Caco-2 cells and Raji B cells) was used.  cDNA array and quantitative RT-PCR showed that mRNA for CD9 was over-expressed.  Immunofluorescence confirmed overexpression of CD9 protein in model FAE as well as in FAE of human ileum and colon.
  • In the human ileum, flux of the protein horseradish peroxidase was seven times higher in the FAE than in villus epithelium, whereas there was no significant difference in paracellular permeability.  Uptake of E. coli was five-fold higher in FAE than in villi.  Comparison between ileum of CD and controls showed significantly increased uptake of bacteria in the FAE of CD.


Conclusions: A defective barrier function in the FAE of rats, induced by stress, alters the immune response to antigens entering via the FAE.  CD9 is a new putative marker for human FAE and may perhaps be used for drug targeting.  The FAE of the human ileum is functionally distinct from regular villus epithelium.  Bacterial transport in the FAE may be altered in CD.

aPrincipal Investigator