Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Published: |
Royal Society
2018
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| _version_ | 1797066484630945792 |
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| author | Muraro, D Parker, A Filippi, S Almet, A Fletcher, A Watson, A Pin, C Maini, P Byrne, H |
| author_facet | Muraro, D Parker, A Filippi, S Almet, A Fletcher, A Watson, A Pin, C Maini, P Byrne, H |
| author_sort | Muraro, D |
| collection | OXFORD |
| description | 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 in ammation. 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 in ammatory 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 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. |
| first_indexed | 2024-03-06T21:42:45Z |
| format | Journal article |
| id | oxford-uuid:487ede2f-9c04-4344-b4b7-3a153c68cecd |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:42:45Z |
| publishDate | 2018 |
| publisher | Royal Society |
| record_format | dspace |
| spelling | oxford-uuid:487ede2f-9c04-4344-b4b7-3a153c68cecd2022-03-26T15:26:10ZChronic TNFα - driven injury delays cell migration to villi in the intestinal epitheliumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:487ede2f-9c04-4344-b4b7-3a153c68cecdSymplectic Elements at OxfordRoyal Society2018Muraro, DParker, AFilippi, SAlmet, AFletcher, AWatson, APin, CMaini, PByrne, HThe 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 in ammation. 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 in ammatory 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 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. |
| spellingShingle | Muraro, D Parker, A Filippi, S Almet, A Fletcher, A Watson, A Pin, C Maini, P Byrne, H Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title | Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title_full | Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title_fullStr | Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title_full_unstemmed | Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title_short | Chronic TNFα - driven injury delays cell migration to villi in the intestinal epithelium |
| title_sort | chronic tnfα driven injury delays cell migration to villi in the intestinal epithelium |
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