Interleukin-21 (IL-21) is a potent cytokine regulating many cell types of the immune system. IL-21 is produced by activated T follicular helper cells (Tfh), Th17 cells, and NKT cells [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]. IL-21 protein 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, 10, 11]. IL-21 blocks the generation of regulatory T cells and their suppressive effects on CD4+ T cells [12, 13]. In addition to its role in T cell biology, IL-21 also plays a critical role in B cell activation, proliferation, differentiation, and apoptosis [2]. IL-21 protein exerts its biological effects through a heterodimeric receptor complex of gamma c and the IL-21-specific IL-21 R [2, 7]. IL-21 is an approximately 14 kDa four-helix-bundle member of 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 R engagement enhances the cytolytic activity and IFN-gamma production of activated NK cells but limits the expansion of resting NK cells [14]. Dysregulation of the IL-21/IL-21 R system contributes to the development of multiple immunological disorders [1, 15]. 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 [16, 17].
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