Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation.

ABSTRACT: The intestinal epithelial monolayer, at the boundary between microbes and the host immune system, plays an important role in the development of inflammatory bowel disease (IBD), particularly as a target and producer of pro-inflammatory TNF. Chronic overexpression of TNF leads to IBD-like pathology over time, but the mechanisms driving early pathogenesis events are not clear. We studied the epithelial response to inflammation by combining mathematical models with in vivo experimental models resembling acute and chronic TNF-mediated injury. We found significant villus atrophy with increased epithelial cell death along the crypt-villus axis, most dramatically at the villus tips, in both acute and chronic inflammation. In the acute model, we observed overexpression of TNF receptor I in the vil

SUBMITTER: Parker A 

PROVIDER: S-EPMC6365534 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature