title: Altered epithelial cell lineage allocation and global expansion of the crypt epithelial stem cell population are associated with ileitis in SAMP1/YitFc mice.
abstract: Crohn's disease is characterized by cycles of mucosal injury and ulceration followed by epithelial regeneration and restoration of normal epithelial function. In this study, we examined whether ileitis in SAMP1/YitFc mice, a recombinant-inbred line that spontaneously develops ileitis resembling human Crohn's disease, was associated with alterations in normal patterns of epithelial differentiation or changes in epithelial regeneration after experimental injury. Increased numbers of Paneth, goblet, and intermediate cells were present focally in the ileum of SAMP1/YitFc mice by 4 weeks of age, before any histological evidence of acute or chronic inflammation. This increase in secretory cells became more pronounced at sites of ileitis with increasing age and inflammation. Additionally, there was mispositioning of Paneth and intermediate cells along the crypt-to-villus unit. A concomitant reduction in the number of absorptive enterocytes was observed. In contrast to the ileal-specific changes in lineage allocation, crypt stem cell numbers began to increase in both the ileum and proximal jejunum at the onset of inflammation in SAMP1/YitFc mice. These data suggest that the alterations in epithelial cell differentiation and increases in the size of the crypt stem cell population observed in SAMP1/YitFc mice are regulated by distinct mechanisms. We speculate that these epithelial alterations may play a role in the pathogenesis of ileitis in this murine model of Crohn's disease.
authors.affiliation: Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Alda
authors.initials: A
authors.lastname: Vidrich
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Buzan
authors.forename: Sean
authors.initials: S
authors.lastname: Barnes
authors.forename: Brian K
authors.initials: BK
authors.lastname: Reuter
authors.forename: Kirstin
authors.initials: K
authors.lastname: Skaar
authors.forename: Chibuzo
authors.initials: C
authors.lastname: Ilo
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
authors.forename: Theresa
authors.initials: T
authors.lastname: Pizarro
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cohn
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects; D019070:Cell Lineage; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D007079:Ileitis / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects