Interleukin-21(IL-21) is an approximately 14 kDa cytokine which belongs to the IL-15/IL-21 family. Mature mouse IL-21 shares 66%,59%, 58%, and 88% aa sequence identity with mature canine, human, rabbit, and rat IL-21, respectively. 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 (IL-21 specific IL-21 R). IL-21 is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer (NK) cells and cytotoxic T cells that can destroy virally infected or cancerous cells. This cytokine induces cell division/proliferation in its target cells. It is required for the migration of dendritic cells to draining lymph nodes .It co-stimulates 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.