The role of IL‐21 in regulating B‐cell function in health and disease

Summary: Interleukin‐21 (IL‐21) belongs to a family of cytokines that includes IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15, all of which bind to private (or shared) receptors as well as the common cytokine receptor γ‐chain as a component. Most cytokines in this family are critically important for both the maintenance and function of T cells and B cells. The receptor for IL‐21 is widely distributed on lymphohematopoietic cells, and IL‐21 plays many biologic roles, including maintenance and function of CD8 + memory T cells and natural killer cells, as well as promoting the generation of Th17 cells in the mouse. One principal non‐redundant role of IL‐21 is the promotion of B‐cell activation, differentiation or death during humoral immune responses. Furthermore, increased IL‐21 production is characteristic of certain autoimmune diseases and is likely to contribute to autoantibody production as well as pathologic features of autoimmune disease. In contrast, IL‐21 may function as a co‐adjuvant to enhance antibody responses and thereby facilitate host defense to malignances and infectious diseases. The critical role of IL‐21 in promoting humoral immune responses makes it an important focus of potential therapeutic interventions in conditions characterized by either overproduction of pathogenic autoantibodies or under production of protective antibodies.