IL-21 (Interleukin-21) is member of the family of cytokines that utilize the common gamma chain as a receptor subunit. This subunit is also a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is produced by activated T follicular helper cells (Tfh), Th17 cells, and NKT cells. It exerts its biological effects through a heterodimeric receptor complex of the common gamma chain and the IL-21-specific IL-21 R. IL-21 supports Tfh cell development, immunoglobulin affinity maturation, plasma cell differentiation, B cell memory responses, and the migration of dendritic cells to draining lymph nodes. It costimulates the activation, proliferation, and survival of CD8+ T cells and NKT cells and promotes Th17 cell polarization. It blocks the generation of regulatory T cells and their suppressive effects on CD4+ T cells. In addition, IL-21 suppresses cutaneous hypersensitivity reactions by limiting allergen-specific IgE production and mast cell degranulation.