Induced Regulatory T Cells: Their Development, Stability, and Applications

iTregs could be a crucial source of regulatory T cells for immune therapy, and clinical applications of iTregs are now ongoing. Reprogramming of effector or memory T cells into iTregs is especially important for overcoming the issue of antigen-specificity, but this requires methods to efficiently and stably generate those cells. Epigenetics plays a key role in Treg development and stability, and methods to affect these marks and enhance the stability of iTregs are under active investigation. pTregs can be induced by some bacterial species, and the microbiota is emerging as an important player in Treg differentiation. Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many facets of immune systems. The transcription factor Foxp3 has been characterized as a master regulator of Tregs, and is induced during their thymic development. Foxp3+ Tregs can also be generated from naïve T cells after stimulation in the presence of TGF-β and IL-2; the resulting cells are called induced Tregs (iTregs) when generated in vitro, or peripheral Tregs (pTregs) when generated in vivo. Compared to tTregs, iTregs have been shown to be unstable, and attempts to generate stable iTregs have been made for clinical applications. We review here the current knowledge on the development of pTregs, iTregs, and their roles and applications. Regulatory T (Treg) cells, as central mediators of immune suppression, play crucial roles in many facets of immune systems. The transcription factor Foxp3 has been characterized as a master regulator of Tregs, and is induced during their thymic development. Foxp3+ Tregs can also be generated from naïve T cells after stimulation in the presence of TGF-β and IL-2; the resulting cells are called induced Tregs (iTregs) when generated in vitro, or peripheral Tregs (pTregs) when generated in vivo. Compared to tTregs, iTregs have been shown to be unstable, and attempts to generate stable iTregs have been made for clinical applications. We review here the current knowledge on the development of pTregs, iTregs, and their roles and applications.