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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Becskei A,Grusby MJ

doi

10.1016/j.febslet.2007.10.007

subject

Has Abstract

pub_date

2007-11-13 00:00:00

pages

5199-206

issue

27

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(07)01064-2

journal_volume

581

pub_type

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