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

Abstract

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 (Teff) and regulatory T-cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity. In this review, we will summarize the current understanding of biomarkers and functions of both forkhead box protein 3 (FoxP3)+ Treg 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 Treg responses and also provide an outlook on the potential of Treg-based immunotherapies in the prevention and treatment of this disease. Discussed immunotherapies include adoptive transfer of ex-vivo expanded FoxP3+ Treg, manipulation of Treg cells via the interleukin (IL)-2/IL-2R pathway and induction of Treg by tolerogenic peptides, tolerogenic dendritic cells or altered gut microbiota.