Abstract:
: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.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Lau KS,Cortez-Retamozo V,Philips SR,Pittet MJ,Lauffenburger DA,Haigis KMdoi
10.1371/journal.pbio.1001393subject
Has Abstractpub_date
2012-01-01 00:00:00pages
e1001393issue
9eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-12-01984journal_volume
10pub_type
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