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Switching gene-regulatory loops in Th1 differentiation
From Q-bio
Edda G. Schulz, Andreas Radbruch, and Thomas Höfer
- Abstract
- In this work we describe a new regulatory principle underlying the differentiation of Th1 lymphocytes. We performed quantitative kinetic measurements to identify new interactions and construct a mathematical model for the expression dynamics of critical genes: (1) the Th1 lineage specifying transcription factor T-bet, (2) the receiver of the Th1 differentiation signal, IL-12 receptor, and (3) the Th1 effector cytokine Interferon-g (Ifn-g). Model-driven experiments showed that instruction for Th1 differentiation is a two-step process. Initial T-bet induction through a sensitive Ifn-g dependent pathway accelerates the response of the slow feedback loop between T-bet and IL-12, active late during differentiation.
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