The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer

IL-21 is a type I cytokine that like IL-2, IL-4, IL-7, IL-9, and IL-15 shares the common cytokine receptor gamma chain, gamma(c). IL-21 is produced by activated CD4(+) T cells, NKT cells, and Th17 cells and has pleiotropic actions on a range of lymphoid lineages. IL-21 regulates immunoglobulin production and drives B cell terminal differentiation into plasma cells, cooperatively expands CD8(+) T cells and drives Th17 differentiation, has inhibitory effects on antigen presentation by dendritic cells, and can be pro-apoptotic for B and NK cells. Moreover, IL-21 has potent anti-tumor effects and is implicated in the development of autoimmune diseases. Regulating IL-21 actions in vivo therefore has clinical potential for a range of diseases and is an area of active investigation.