Interleukin-2 and regulatory T cells in rheumatic diseases

Failure of regulatory T (T-reg) cells to properly control immune responses leads invariably to autoimmunity and organ damage. Decreased numbers or impaired function of T-reg cells, especially in the context of inflammation, has been documented in many human autoimmune diseases. Restoration of T-reg cell fitness and/or expansion of their numbers using low-dose natural IL-2, the main cytokine driving T-reg cell survival and function, has demonstrated clinical efficacy in early clinical trials. Genetically modified IL-2 with an extended half-life and increased selectivity for T-reg cells is now in clinical development. Administration of IL-2 combined with therapies targeting other pathways involved in the expression of autoimmune diseases should further enhance its therapeutic potential. Ongoing clinical efforts that capitalize on the early clinical success of IL-2 treatment should bring the use of this cytokine to the forefront of biological treatments for autoimmune diseases. Regulatory T (T-reg) cells have crucial roles in peripheral tolerance and limiting inflammation, and IL-2 is an important cytokine for T-reg cell differentiation, activity and homeostasis. In this Review, Kolios, Tsokos and Klatzmann provide an overview of T-reg cell and IL-2 involvement in rheumatic diseases and how modulating IL-2 signalling and T-reg cell biology might provide novel treatment avenues.