A network model for the control of the differentiation process in Th cells

T helper cells differentiate from a precursor type, Th0, to either the Th1 or Th2 phenotypes. While a number of molecules are known to participate in this process, it is not completely understood how they regulate each other to ensure differentiation. This article presents the core regulatory network controlling the differentiation of Th cells, reconstructed from published molecular data. This network encompasses 17 nodes, namely IFN-gamma, IL-4, IL-12, IL-18. IFN-beta, IFN-gamma R, IL-4R, IL-12R, IL-18R, IFN-beta R, STAT-1, STAT 6, STAT-4, IRAK, SOCS-1, GATA-3, and T-bet, as well as their cross-regulatory interactions. The reconstructed network was modeled as a discrete dynamical system, and analyzed in terms of its constituent feedback loops. The stable steady states of the Th network model are consistent with the stable molecular patterns of activation observed in wild type and mutant Th0, Th1 and Th2 cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved.