The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg signature. Computational network inference and experimental testing assessed the contribution of other transcription factors (TF). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability.

Synthetic biology is an emerging field focused on engineering biomolecular systems and cellular capabilities for a variety of applications. Substantial progress began a little over a decade ago with the creation of synthetic gene networks inspired by electrical engineering. Since then, the field has designed and built increasingly complex circuits and constructs and begun to use these systems in a variety of settings, including the clinic. These efforts include the development of synthetic biology therapies for the treatment of infectious diseases and cancer, as well as approaches in vaccine development, microbiome engineering, cell therapy, and regenerative medicine. Here, we highlight advances in the biomedical application of synthetic biology and discuss the field's clinical potential.