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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Autores principales:	Ken S Lau, Virna Cortez-Retamozo, Sarah R Philips, Mikael J Pittet, Douglas A Lauffenburger, Kevin M Haigis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d1766cb9d5cd45989788fac10b361db7
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spelling	oai:doaj.org-article:d1766cb9d5cd45989788fac10b361db72021-11-18T05:37:25ZMulti-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.1544-91731545-788510.1371/journal.pbio.1001393https://doaj.org/article/d1766cb9d5cd45989788fac10b361db72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23055830/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Intestinal 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.Ken S LauVirna Cortez-RetamozoSarah R PhilipsMikael J PittetDouglas A LauffenburgerKevin M HaigisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 9, p e1001393 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ken S Lau Virna Cortez-Retamozo Sarah R Philips Mikael J Pittet Douglas A Lauffenburger Kevin M Haigis Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.
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.
format	article
author	Ken S Lau Virna Cortez-Retamozo Sarah R Philips Mikael J Pittet Douglas A Lauffenburger Kevin M Haigis
author_facet	Ken S Lau Virna Cortez-Retamozo Sarah R Philips Mikael J Pittet Douglas A Lauffenburger Kevin M Haigis
author_sort	Ken S Lau
title	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_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_sort	multi-scale in vivo systems analysis reveals the influence of immune cells on tnf-α-induced apoptosis in the intestinal epithelium.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d1766cb9d5cd45989788fac10b361db7
work_keys_str_mv	AT kenslau multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium AT virnacortezretamozo multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium AT sarahrphilips multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium AT mikaeljpittet multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium AT douglasalauffenburger multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium AT kevinmhaigis multiscaleinvivosystemsanalysisrevealstheinfluenceofimmunecellsontnfainducedapoptosisintheintestinalepithelium
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Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

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