Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

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 Biol

journal_title

PLoS biology

authors

Lau KS,Cortez-Retamozo V,Philips SR,Pittet MJ,Lauffenburger DA,Haigis KM

doi

10.1371/journal.pbio.1001393

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

e1001393

issue

9

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-12-01984

journal_volume

10

pub_type

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