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 β-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.