Treg stability: to be or not to be

Regulatory T cell (T-reg) stability has been primarily determined by the maintained expression of the transcription factor Forkhead box P3 (Foxp3). However, T-regs can exhibit instability while maintaining Foxp3 expression, requiring a re-examination of what defines T-reg stability. Recent work suggests that the establishment and stability of T-regs is mediated by a number of mechanisms besides Foxp3 expression, such as epigenetic modifications, Foxo1/3a localization, expression of Eos and signaling via Neuropilin-1. Additional studies may help to define approaches that can undermine T-reg stability in cancer or enhance T-reg stability in transplantation, autoimmune or inflammatory diseases and therefore have substantial therapeutic utility. In this review, we will discuss how T-reg stability is defined and the mechanisms utilized to maintain stability.