Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium
Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Mul...
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PLoS Computational Biology
2013
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| 在线阅读: | http://hdl.handle.net/1721.1/76238 |
| _version_ | 1826205853641867264 |
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| author | Cortez-Retamozo, Virna Philips, Sarah R. Pittet, Mikael J. Haigis, Kevin M. Lau, Ken S. Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Cortez-Retamozo, Virna Philips, Sarah R. Pittet, Mikael J. Haigis, Kevin M. Lau, Ken S. Lauffenburger, Douglas A |
| author_sort | Cortez-Retamozo, Virna |
| collection | MIT |
| description | Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting. |
| first_indexed | 2024-09-23T13:20:09Z |
| format | Article |
| id | mit-1721.1/76238 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:20:09Z |
| publishDate | 2013 |
| publisher | PLoS Computational Biology |
| record_format | dspace |
| spelling | mit-1721.1/762382022-10-01T14:36:00Z Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium Cortez-Retamozo, Virna Philips, Sarah R. Pittet, Mikael J. Haigis, Kevin M. Lau, Ken S. Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Lau, Ken Siu-Kwong Lauffenburger, Douglas A. Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting. 2013-01-10T17:56:22Z 2013-01-10T17:56:22Z 2012-09 2012-05 Article http://purl.org/eprint/type/JournalArticle 1545-7885 1544-9173 http://hdl.handle.net/1721.1/76238 Lau, Ken S. et al. “Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium.” Ed. Jerry R. McGhee. PLoS Biology 10.9 (2012): e1001393. en_US http://dx.doi.org/10.1371/journal.pbio.1001393 PLoS Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf PLoS Computational Biology PLoS |
| spellingShingle | Cortez-Retamozo, Virna Philips, Sarah R. Pittet, Mikael J. Haigis, Kevin M. Lau, Ken S. Lauffenburger, Douglas A Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title | Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title_full | Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title_fullStr | Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title_full_unstemmed | Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title_short | Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium |
| title_sort | multi scale in vivo systems analysis reveals the influence of immune cells on tnf α induced apoptosis in the intestinal epithelium |
| url | http://hdl.handle.net/1721.1/76238 |
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