Muraro, D. orcid.org/0000-0001-9601-237X, Parker, A., Vaux, L. et al. (7 more authors) (2018) Chronic TNFα-driven injury delays cell migration to villi in the intestinal epithelium. Interface, 15 (145). 20180037. ISSN 1742-5689
Abstract
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 mechanisms 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 TNFα-driven epithelial cell death. Parameter inference reveals that acute inflammatory cell death has a transient effect on epithelial cell dynamics, whereas cell death caused by chronic elevated TNFα causes a delay in the accumulation of labelled cells onto the villus compared to the 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Author(s). This is an author produced version of a paper subsequently published in Interface. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | cell migration; cell-based model; compartmental model; intestinal crypts |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Aug 2018 10:01 |
Last Modified: | 30 Aug 2018 03:36 |
Published Version: | https://doi.org/10.1098/rsif.2018.0037 |
Status: | Published |
Publisher: | The Royal Society |
Refereed: | Yes |
Identification Number: | 10.1098/rsif.2018.0037 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:135056 |