A Minimal Transcriptional Controlling Network of Regulatory T Cell Development

Regulatory T cells (Treg) are a subpopulation of T cells that are central to immune homeostasis and develop under the control of a complex regulatory network consisting of FoxP3 and its partner factors. A central question about this network is how does it enable T cells to robustly specify and stably maintain their states despite intrinsic and environmental fluctuations. Inspired by recent experimental advances, we propose here a minimal transcriptional controlling network and use it to illustrate the robustness and dynamic features of Treg development. Our study shows that the controlling network may exhibit distinct dynamics depending on its parameter regimes and that the maintenance of multistability requires the orchestration of both its positive and negative feedback loops. In addition, system volume contributes monotonically to the increase in the network's robustness. We further show that the dynamics of our model varies with the alteration of FoxP3-DNA binding affinity, consistent with recent experimental findings. This minimal model thereby offers new insights into the dynamics and robustness of Treg development and may serve as a platform for future exploration toward a more quantitative and systematic understanding of the immune system.