Advances in IL-21 biology - enhancing our understanding of human disease

Cytokines play critical roles in regulating the development and function of immune cells. Cytokines function by binding specific multimeric receptor complexes and activating intracellular signaling pathways that often involve JAKs and STATs. In addition to contributing to immunity, when production of cytokines is perturbed, they can contribute to disease. IL-21 is a pleiotropic cytokine produced predominantly by CD4+ T cells and NKT cells. Gene-targeting studies in mice and in vitro analyses of human and murine lymphocytes have revealed central roles of IL-21 in regulating effector functions of T cells, NK cells and B cells. However, recent discoveries of loss-of function mutations in IL21 or IL21R in humans have unveiled unexpected roles for IL-21 in immune regulation. This review will focus on recent advances in IL-21 biology that have highlighted its critical role in normal immunity and how dysregulated IL-21 production can lead to immunodeficiency and autoimmune conditions.