IL-21 is a type I cytokine produced by T cells and natural killer T cells that
has pleiotropic actions on a wide range of immune and non-immune cell types.
Since its discovery in 2000, extensive studies on the biological actions of IL-21
have been performed in vitro and in vivo. Recent reports describing patients with
primary immunodeficiency caused by mutations of IL21 or IL21R have further
deepened our knowledge of the role of this cytokine in host defense. Elucidation
of the molecular mechanisms that mediate IL-21's actions has provided the
rationale for targeting IL-21 and IL-21 downstream mediators for therapeutic
purposes. The use of next-generation sequencing technology has provided further
insights into the complexity of IL-21 signaling and has identified transcription
factors and co-factors involved in mediating the actions of this cytokine. In
this review, we discuss recent advances in the biology and signaling of IL-21 and
how this knowledge can be potentially translated into clinical settings.
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