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

Summary: Type 1 diabetes (T1D) is a T‐cell‐mediated autoimmune disease resulting in islet <italic>β</italic>‐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 <italic>ex‐vivo</italic> 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. [ABSTRACT FROM AUTHOR]