Heterogeneity and Stability in Foxp3+ Regulatory T Cells

Foxp3+ regulatory T cells (Tregs) play an indispensable role in controlling tolerance and immunity against self- and foreign antigens. The failure of Tregs to properly function is the direct cause of systemic and chronic inflammation as well as immune suppression. It is now evident that Tregs are highly heterogeneous populations depending on the surface phenotypes, cytokine profiles, and anatomical locations. Yet, our understanding of the cellular and molecular pathways underlying such heterogeneity is very limited. Furthermore, some Tregs lose the phenotype (and suppressive functions) and instead acquire pathogenicity. Since utilizing Tregs as a tool for immunotherapy is being implemented in many clinical settings, it is of utmost importance to understand the precise mechanisms by which the loss of Treg phenotype (and function) is prevented. In this review, both cellular and molecular factors involved in Treg heterogeneity and stability are discussed.