Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier

Forkhead box P3-expressing regulatory T (Treg) cells are essential for self-tolerance, with an emerging role in tissue repair and regeneration. Their ability to traffic to tissue and perform complex therapeutic tasks in response to the tissue microenvironment make them an attractive candidate for drug development. Early experiences of Treg cell therapy in patients with graft-versus-host disease, type 1 diabetes, and organ transplantation have shown that it is feasible, safe, and potentially efficacious in some settings. Many ongoing trials in patients with a wide variety of diseases will further enhance our knowledge about the optimal approaches for Treg cell manufacturing and dosing. We review the current preclinical rationale supporting Treg cell therapy in a variety of disease settings ranging from tissue transplantation, autoimmune diseases, and non-immune-mediated inflammatory settings. We point out challenges in development of Treg cell therapy and speculate how synthetic biology can be used to enhance the feasibility and efficacy of Treg cell therapy for autoimmune and autoinflammatory diseases.