Treg stability: to be or not to be

Regulatory T cell (Treg) stability has been primarily determined by the maintained expression of the transcription factor Forkhead box P3 (Foxp3). However, Tregs can exhibit instability while maintaining Foxp3 expression, requiring a re-examination of what defines Treg stability. Recent work suggests that the establishment and stability of Tregs 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 Treg stability in cancer or enhance Treg stability in transplantation, autoimmune or inflammatory diseases and therefore have substantial therapeutic utility. In this review, we will discuss how Treg stability is defined and the mechanisms utilized to maintain stability.