Overview of IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types
Interleukin-21 (IL-21) is the most recently described cytokine belonging to the common cytokine receptor gamma-chain family. Like other common gamma chain family members, IL-21 is a four alpha-helix bundle type I cytokine. It signals through a receptor complex consisting of IL-21 R and common gamma-chain/IL-2 R gamma. IL-21 is produced primarily by CD4+ T cells and natural killer T (NKT) cells and has a broad range of effects on a number of different cell types. IL-21 signaling in CD4+ T cells is required for both Th17 differentiation and the generation of T follicular helper (Tfh) cells, which support B cell differentiation and antibody production in germinal centers. IL-21 also directly regulates B cell proliferation and apoptosis in a context-dependent manner and can promote immunoglobulin production and isotype class switching. In addition, IL-21 signaling enhances the cytotoxicity of CD8+ T cells, natural killer cells, and NKT cells.