Interleukin-21 (IL-21) is a type I cytokine that modulates functions of T, B, natural killer (NK), and myeloid cells. IL-21 is produced by activated T follicular helper cells (Tfh), Th17 cells, and NKT cells. Tfh-derived IL-21 plays an important role in the development of humoral immunity through its autocrine effects on the Tfh cell and paracrine effects on immunoglobulin affinity maturation, plasma cell differentiation, and B cell memory responses.The 133 amino acid (aa) mature human IL-21 protein shares 63% and 61% aa sequence identity with mouse and rat IL-21 protein, respectively. Alternative splicing generates an additional isoform with a substitution of the C-terminal 16 amino acids. IL-21 shows having much relation with clinical illnesses, including cancer immunotherapy, viral infections and allergies. And it suppresses cutaneous hypersensitivity reactions by limiting allergen-specific IgE production and mast cell degranulation.