Interleukin-21 (IL-21) is an approximately 14 kDa four-helix-bundle cytokine in the family of cytokines that utilize the common gamma chain ( gamma c) as a receptor subunit. gamma c is also a subunit of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 (1). IL-21 is produced by activated T follicular helper cells (Tfh), Th17 cells, and NKT cells (2-6). It exerts its biological effects through a heterodimeric receptor complex of gamma c and the IL-21-specific IL-21 R (2, 7). 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 (4, 8, 9). It is also required for the migration of dendritic cells to draining lymph nodes (10). IL-21 regulates several aspects of T cell function. It co?stimulates the activation, proliferation, and survival of CD8+ T cells and NKT cells and promotes Th17 cell polarization (3, 5, 6, 11, 12). It blocks the generation of regulatory T cells and their suppressive effects on CD4+ T cells (13, 14). IL-21 R engagement enhances the cytolytic activity and IFN-gamma production of activated NK cells but limits the expansion of resting NK cells (15). In addition, IL-21 suppresses cutaneous hypersensitivity reactions by limiting allergen-specific IgE production and mast cell degranulation (16). Dysregulation of the IL?21/IL?21 R system contributes to the development of multiple immunological disorders (1, 17). The mouse IL?21 precursor contains a predicted 17 amino acid (aa) signal sequence and a 129 aa mature chain. Mature mouse IL-21 shares 66%, 59%, 58%, and 88% aa sequence identity with mature canine, human, rabbit, and rat IL-21, respectively.
