Stabilizing human regulatory T cells for tolerance inducing immunotherapy

Many autoimmune diseases develop as a consequence of an altered balance between autoreactive immune cells and suppressive FOXP3+ Treg. Restoring this balance through amplification of Treg represents a promising strategy to treat disease. However, FOXP3+ Treg might become unstable especially under certain inflammatory conditions, and might transform into proinflammatory cytokine-producing cells. The issue of heterogeneity and instability of Treg has caused considerable debate in the field and has important implications for Treg-based immunotherapy. In this review, we discuss how Treg stability is defined and what the molecular mechanisms underlying the maintenance of FOXP3 expression and the regulation of Treg stability are. Also, we elaborate on current strategies used to stabilize human Treg for clinical purposes. This review focuses on human Treg, but considering that cell-intrinsic mechanisms to regulate Treg stability in mice and in humans might be similar, data derived from mice studies are also disc...