Emerging mechanisms and applications of low-dose IL-2 therapy in autoimmunity.

Interleukin 2 (IL-2) is a pleiotropic cytokine that elicits both immunogenic and tolerogenic immune response essential for homeostasis. Initial clinical application of IL-2 based therapy was hampered by its function on broad spectrum of cells expressing corresponding receptors, which exerts uncontrolled side effects in clinical trials. While recent progress on structural modification or adjusted regimen of IL-2, revolutionized the use of IL-2 in immunomodulation process that requires stringent selection of effector cells, such as promotion of T REG cells for tolerance or invigoration of CD8+ T cells against infection and cancer. Low-dose IL-2 therapy is amongst these succuss and is proved to be a promising immunotherapy to treat a broad range of autoimmune and inflammatory diseases. This article will review major recent advances in fundamental research on IL-2 as well as significant progress made in clinical trials where patients received low-dose IL-2 therapy. This knowledge also helps design further optimized IL-2 therapies for a broader application in treating human disease. [Display omitted] • Low-dose IL-2 therapy is an emerging immunotherapy to treat a broad range of autoimmune and inflammatory diseases. • These autoimmune and inflammatory diseases include systemic lupus erythematosus, type 1 diabetes and rheumatoid arthritis. • Clinical trials demonstrated the safety and efficacy of low-dose IL-2 therapy in patients with autoimmune diseases. • The repurpose of IL-2 therapy with a lower to ultra-dose in autoimmunity was largely based on the selective promotion of T REG cells for tolerance. • New human and mouse studies found that low-dose IL-2 treatment inhibits the generation of autoreactive T FH and T H 17 cells [ABSTRACT FROM AUTHOR]