IL21

Interleukin-21 (IL-21) is a cytokine of the interleukin-2 (IL-2) family that participates in the regulation of adaptive immunity. It is produced primarily by activated CD4+ T cells and by natural killer T (NKT) cells, and acts on multiple immune cell types.

IL-21 signals through its receptor, IL-21R, which forms a complex with the common gamma chain (CD132). Ligand binding activates the JAK/STAT pathway, predominantly JAK1 and JAK3 with downstream STAT1, STAT3 and STAT5, leading to changes in gene expression.

Biologically, IL-21 promotes differentiation of B cells into antibody-secreting plasma cells, supports class-switch recombination to IgG and IgA, and enhances humoral responses. It also stimulates natural killer (NK) cell and cytotoxic CD8+ T cell activity and can influence helper T cell differentiation, especially promoting T follicular helper cell responses.

In health and disease, IL-21 contributes to responses against infections and tumors and has been studied as an immunotherapeutic agent and vaccine adjuvant. Elevated IL-21 levels have been associated with autoimmune conditions in animal models and humans, highlighting a context-dependent, potentially proinflammatory role.

Genetics and expression: the IL21 gene encodes the cytokine and is expressed by activated T cells and other immune cells; its receptor IL21R is widely expressed on B cells, T cells, NK cells and dendritic cells, enabling broad immunomodulatory effects.