Harnessing the power of regulatory T-cells to control autoimmune diabetes: overview and perspective

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease resulting in islet beta-cell destruction, hypoinsulinaemia and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T-cells (T-eff) and regulatory T-cells (T-reg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of T-reg in the hope of specifically hampering the pathogenic T-eff activity. In this review, we will summarize the current understanding of biomarkers and functions of both forkhead box protein 3 (FoxP3)(+) T-reg and type 1 regulatory T (Tr1) cells in health and in T1D, examine the outcome of experimental therapies in both animal models and humans via manipulation of T-reg responses and also provide an outlook on the potential of T-reg-based immunotherapies in the prevention and treatment of this disease. Discussed immunotherapies include adoptive transfer of ex-vivo expanded FoxP3(+) T-reg, manipulation of T-reg cells via the interleukin (IL)-2/IL-2R pathway and induction of T-reg by tolerogenic peptides, tolerogenic dendritic cells or altered gut microbiota.