RT Journal Article
SR Electronic
T1 Chronic inflammation delays cell migration to villi in the intestinal epithelium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 248344
DO 10.1101/248344
A1 Daniele Muraro
A1 Aimee Parker
A1 Laura Vaux
A1 Sarah Filippi
A1 Alexander G. Fletcher
A1 Alastair J. Watson
A1 Carmen Pin
A1 Philip K. Maini
A1 Helen M. Byrne
YR 2018
UL http://biorxiv.org/content/early/2018/01/15/248344.abstract
AB The intestinal epithelium is a single layer of cells which provides the first line of defence of the intestinal mucosa to bacterial infection. Cohesion of this physical barrier is supported by renewal of epithelial stem cells, residing in invaginations called crypts, and by crypt cell migration onto protrusions called villi; dysregulation of such mechanism may render the gut susceptible to chronic inflammation. The impact that excessive or misplaced epithelial cell death may have on villus cell migration is currently unknown. We integrated cell-tracking methods with computational models to determine how epithelial homeostasis is affected by acute and chronic inflammatory cell death. Parameter inference reveals that acute inflammatory cell death has a transient effect on epithelial cell dynamics, whereas cell death caused by chronic inflammation causes a delay in the accumulation of labelled cells onto the villus compared to control. Such a delay may be reproduced by using a cell-based model to simulate the dynamics of each cell in a crypt-villus geometry, showing that a prolonged increase in cell death slows the migration of cells from the crypt to the villus. This investigation highlights which injuries (acute or chronic) may be regenerated and which cause disruption of healthy epithelial homeostasis.