UZH-Logo

Maintenance Infos

Contribution of IL-12R mediated feedback loop to Th1 cell differentiation


Becskei, A; Grusby, M J (2007). Contribution of IL-12R mediated feedback loop to Th1 cell differentiation. FEBS Letters, 581(27):5199-5206.

Abstract

T helper 1 (Th1) cell fate is induced by overlapping signaling pathways, whose kinetic principles and regulatory motifs are largely unknown. We identified a simple positive feedback loop in the STAT4 signaling pathway, whereby activation by IL-12 leads to the increased expression in IL-12 receptor. A computational analysis shows that this feedback loop synergizes with the one mediated by the IFN-gamma secreted by differentiating cells, when the induction of Th1 cell fate is weak. Positive feedback loops are often utilized to enhance phenotypic differentiation. This effect was confirmed by experiments showing that stochastic fluctuations in the expression of IL-12 receptor gene were amplified, leading to two discrete levels of expression in a cell population.

Abstract

T helper 1 (Th1) cell fate is induced by overlapping signaling pathways, whose kinetic principles and regulatory motifs are largely unknown. We identified a simple positive feedback loop in the STAT4 signaling pathway, whereby activation by IL-12 leads to the increased expression in IL-12 receptor. A computational analysis shows that this feedback loop synergizes with the one mediated by the IFN-gamma secreted by differentiating cells, when the induction of Th1 cell fate is weak. Positive feedback loops are often utilized to enhance phenotypic differentiation. This effect was confirmed by experiments showing that stochastic fluctuations in the expression of IL-12 receptor gene were amplified, leading to two discrete levels of expression in a cell population.

Citations

18 citations in Web of Science®
21 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 13 Jul 2010
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, not refereed, original work
Communities & Collections:08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2007
Deposited On:13 Jul 2010 06:54
Last Modified:05 Apr 2016 14:10
Publisher:Elsevier
ISSN:0014-5793
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.febslet.2007.10.007
PubMed ID:17950290

Download

[img]
Filetype: PDF - Registered users only
Size: 831kB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations