ABSTRACT
Interleukin-21 (IL-21) is a four a-helical bundle type I cytokine that is produced by CD4+ T cells and has actions on T, B, natural killer (NK), and myeloid cells.1,2 IL-21 binds to a receptor that comprises IL-21R and the common cytokine receptor g chain, gc, the protein that is mutated in patients with X-linked severe combined immunodeficiency (XSCID).1,3 In XSCID, T cells and NK cells are absent or profoundly decreased in number and B cells are present but not functional. gc is also a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 (Figure 17.1). The actions of all six gc family cytokines are summarized in Table 17.1. The defective T-cell and NK-cell development are due substantially to defective signaling by IL-7 and IL-15, respectively. We discuss herein that IL-21 is important for T, B, NK, and myeloid cell biology. Interestingly, depending on the target cell and stimulation context, IL-21 can be pro-apoptotic or can promote the differentiation and/or proliferation of target cells. In particular, IL-21 can potently augment T-cell proliferation and the expansion of CD8+ T cells, can drive B-cell differentiation to memory cells and terminally differentiated plasma cells, has anti-tumor
actions, and is implicated as playing a role in the development of autoimmunity. As such, IL-21 is a pleiotropic cytokine with diverse immunomodulatory actions. Although more development is needed, based on animal studies, IL-21 has the potential to be of clinical importance, where either increasing or decreasing its activities may be therapeutically useful depending on the clinical setting.
